Case and Research Letter
Bullous and Non-Bullous Lichen Planus During Anti PD-1 Therapy for Lung Cancer
Liquen plano bulloso y no-ampolloso durante la terapia anti PD-1 para el cáncer de pulmón
Department of Dermatology, Fukushima Medical University, Fukushima, Japan
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B)<span class="elsevierStyleHsp" style=""></span>Las características histológicas revelaron proliferación epidérmica irregular con edema subepidérmico e infiltrados celulares en la dermis superior. Tinción hematoxilina-eosina (HE), ×100. C)<span class="elsevierStyleHsp" style=""></span>Ampliación máxima que muestra degeneración de la licuefacción de las capas epidérmicas basales. HE, ×200. Las células infiltrantes fueron inmunorreactivas para CD4, ×200 (D) y CD8, ×200 (E). gr1.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Y. Hanami, T. Yamamoto" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Y." "apellidos" => "Hanami" ] 1 => array:2 [ "nombre" => "T." 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Tirelli, A. Alfaro, G. Citera, C.M. Echeverría" "autores" => array:4 [ 0 => array:2 [ "nombre" => "L.L." "apellidos" => "Tirelli" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Alfaro" ] 2 => array:2 [ "nombre" => "G." "apellidos" => "Citera" ] 3 => array:2 [ "nombre" => "C.M." "apellidos" => "Echeverría" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731022008237?idApp=UINPBA000044" "url" => "/00017310/0000011300000010/v1_202211300529/S0001731022008237/v1_202211300529/es/main.assets" ] "asociados" => array:1 [ 0 => array:19 [ "pii" => "S0001731022008419" "issn" => "00017310" "doi" => "10.1016/j.ad.2022.10.018" "estado" => "S300" "fechaPublicacion" => "2022-11-01" "aid" => "3240" "copyright" => "AEDV" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "Actas Dermosifiliogr. 2022;113:T1014-T1016" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "es" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta científico-clínica</span>" "titulo" => " Liquen plano bulloso y no-ampolloso durante la terapia anti PD-1 para el cáncer de pulmón" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "T1014" "paginaFinal" => "T1016" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Bullous and Non-Bullous Lichen Planus During Anti PD-1 Therapy for Lung Cancer" ] ] "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" => 1006 "Ancho" => 1305 "Tamanyo" => 348821 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A)<span class="elsevierStyleHsp" style=""></span>Placas queratósicas violáceas diseminadas en la parte baja de la pierna. B)<span class="elsevierStyleHsp" style=""></span>Las características histológicas revelaron proliferación epidérmica irregular con edema subepidérmico e infiltrados celulares en la dermis superior. Tinción hematoxilina-eosina (HE), ×100. C)<span class="elsevierStyleHsp" style=""></span>Ampliación máxima que muestra degeneración de la licuefacción de las capas epidérmicas basales. HE, ×200. Las células infiltrantes fueron inmunorreactivas para CD4, ×200 (D) y CD8, ×200 (E). gr1.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Y. Hanami, T. Yamamoto" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Y." "apellidos" => "Hanami" ] 1 => array:2 [ "nombre" => "T." "apellidos" => "Yamamoto" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731022008419?idApp=UINPBA000044" "url" => "/00017310/0000011300000010/v1_202211300529/S0001731022008419/v1_202211300529/es/main.assets" ] ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case and Research Letter</span>" "titulo" => "Bullous and Non-Bullous Lichen Planus During Anti PD-1 Therapy for Lung Cancer" "tieneTextoCompleto" => true "saludo" => "Dear Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "1014" "paginaFinal" => "1016" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Y. Hanami, T. Yamamoto" "autores" => array:2 [ 0 => array:4 [ "nombre" => "Y." "apellidos" => "Hanami" "email" => array:1 [ 0 => "yuka-66@fmu.ac.jp" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "T." "apellidos" => "Yamamoto" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Department of Dermatology, Fukushima Medical University, Fukushima, Japan" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Liquen plano bulloso y no-ampolloso durante la terapia anti PD-1 para el cáncer de pulmón" ] ] "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" => 977 "Ancho" => 1305 "Tamanyo" => 367289 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">(A) Multiple, well-defined dark-red erythematous plaques with scales on the lower thighs. (B, C) Histological features showing focal hyperkeratosis with orthokeratosis, hyperplasia of the granular layer, irregular epidermal hyperproliferation, mild liquefaction degeneration of the basal layers, and edema of dermal papillae. HE, (B) ×100, (C) ×200. Infiltrating cells were immunoreactive for CD4, ×200 (D) and CD8, ×200 (E).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Several types of cutaneous adverse reaction have been reported during anti-programmed cell death (PD)-1 antibody therapy. We describe herein rare cases of lichen planus (LP) which developed during nivolumab therapy for advanced non-small-cell lung cancer (NSCLC). Both cases involved the lower extremities, and one of which was bullous LP.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Case 1: A 74-year-old female was referred to the Department of Dermatology at Shirakawa Kosei General Hospital, complaining of skin rashes on the lower extremities. She was not taking any medications. She had been treated with nivolumab (3<span class="elsevierStyleHsp" style=""></span>mg/kg) administration every two weeks for NSCLC. After the third infusion, itchy eruptions appeared on the lower extremities. Physical examination showed multiple well-defined, purple-colored keratotic plaques slightly covered with scales on the bilateral lower extremities (<a class="elsevierStyleCrossRef" href="#fig1">Fig. 1</a>A). Histological examination showed focal hyperkeratosis with parakeratosis, focal loss of the granular layer, irregular epidermal hyperproliferation, and mild liquefaction degeneration of the basal layers of the epidermis with prominent subepidermal edema (<a class="elsevierStyleCrossRef" href="#fig1">Fig. 1</a>B, C). Mononuclear cells, which were mainly composed of CD4- and CD8-positive T-cells, infiltrated into the upper dermis (<a class="elsevierStyleCrossRef" href="#fig1">Fig. 1</a>D, E). Direct immunofluorescence was negative for either immunoglobulins or C3 deposition in the epidermal basement membrane. She was thereafter treated with topical corticosteroids without discontinuation of nivolumab, but with insufficient effects.</p><elsevierMultimedia ident="fig1"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Case 2: An 81-year-old man was treated with pembrolizumab (3<span class="elsevierStyleHsp" style=""></span>mg/kg) administration every three weeks for NSCLC. After the ninth infusion, he was referred to the Department of Dermatology at Fukushima Medical University Hospital, complaining of itchy skin rashes on the lower extremities. After the twelfth infusion, erythema and multiple well-defined dark-red plaques slightly covered with scales appeared on the lower thighs (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A). Histological examination showed focal hyperkeratosis with orthokeratosis, hyperplasia of the granular layer, irregular epidermal hyperproliferation, mild liquefaction degeneration of the basal layers, and edema of dermal papillae (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>B, C). A band-like infiltrate of inflammatory cells, mainly composed of CD4- and CD8-positive T-cells, was observed in the upper dermis (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>D, E). He was treated with topical corticosteroids and oral antihistamine without discontinuation of pembrolizumab, which resulted in satisfactory effects.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">To date, cases of exacerbation of pre-existing psoriasis or de novo induction of psoriasis/psoriasiform eruptions have been reported during nivolumab therapy; however, induction of LP is rare. There are several reports on LP or lichenoid dermatitis.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1–6</span></a> In a single institution cohort study, lichenoid reactions were observed in 17% of 82 patients with metastatic melanoma who received anti-PD-1 therapy.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Histopathologically, the degree of interface dermatitis and epidermal changes are variable. Bullous LP is commonly seen on the lower extremities. Histopathologically, biopsy from the bullous lesion is characterized by a subepidermal bulla accompanied by classical changes of LP. Bulla formation may be due to the extensive liquefaction and vacuolation of the basal layer. In Case 1, purple-colored keratotic plaques appeared on the lower legs after the initiation of nivolumab. Histopathological examination revealed irregular hyperproliferation of the epidermis with marked subepidermal edema. Wakade et al.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> reported three cases of PD-1 inhibitor (pembrolizumab) induced bullous LP-like reactions after 2–22 cycles of administration. Two of the patients had NSCLC, and the other had melanoma. Biolo et al.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> recently reported an unusual case of linear bullous LP unilaterally involved the lower extremity under treatment with nivolumab.</p><p id="par0025" class="elsevierStylePara elsevierViewall">It has been suggested that the pathogenesis of LP is due to epidermal damage caused by autoreactive cytotoxic CD8+ T-cells, mediated by interferon-γ (IFN-γ). In murine LP models, prominent expression of PD-L1 in keratinocytes is suggested to play a protective role against cytotoxic CD8+ T-cells.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> In addition, in vitro studies showed that administration of anti-PD-1 antibodies induced increased production of IFN-γ from peripheral blood mononuclear cells of patients with oral LP.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> Komori et al. recently reported a case which developed LP focally in an irradiated area, suggesting Koebner phenomenon.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> They speculated a close relationship between anti-PD-1 therapy plus radiotherapy and the development of LP. Another recent report showed an increased mRNA expression of granzyme B and IFN-γ after nivolumab treatment.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> Inhibition of PD-1 may induce epidermal basal layer damage with prominent edema leading to bullous LP, mediated by IFN-γ and other molecules.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interest</span><p id="par0030" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest directly relevant to the content of this article.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1006 "Ancho" => 1305 "Tamanyo" => 348821 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Purple-colored keratotic plaques scattered on the lower leg. (B) Histological features showing irregular epidermal proliferation with subepidermal edema and cellular infiltrates in the upper dermis. Hematoxylin–eosin stain [HE], ×100. (C) Higher magnification showing liquefaction degeneration of the basal layers of the epidermis. HE, ×200. Infiltrating cells were immunoreactive for CD4, ×200 (D) and CD8, ×200 (E).</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" => 977 "Ancho" => 1305 "Tamanyo" => 367289 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">(A) Multiple, well-defined dark-red erythematous plaques with scales on the lower thighs. (B, C) Histological features showing focal hyperkeratosis with orthokeratosis, hyperplasia of the granular layer, irregular epidermal hyperproliferation, mild liquefaction degeneration of the basal layers, and edema of dermal papillae. HE, (B) ×100, (C) ×200. Infiltrating cells were immunoreactive for CD4, ×200 (D) and CD8, ×200 (E).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cutaneous adverse events (AEs) of anti-programmed cell death (PD)-1 therapy in patients with metastatic melanoma: a single-institution cohort" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.J.E. Hwang" 1 => "G. Carlos" 2 => "D. Wakade" 3 => "K. Byth" 4 => "B.Y. Kong" 5 => "S. 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Gilstrap" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1158/2326-6066.CIR-14-0134" "Revista" => array:6 [ "tituloSerie" => "Cancer Immunol Res" "fecha" => "2015" "volumen" => "3" "paginaInicial" => "18" "paginaFinal" => "22" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25287118" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0070" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nivolumab reactivation of hypertrophic lichen planus, a case report and review of published literature" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M. Maarouf" 1 => "C. Alexander" 2 => "V.Y. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 16 | 6 | 22 |
| 2024 October | 82 | 53 | 135 |
| 2024 September | 95 | 40 | 135 |
| 2024 August | 105 | 58 | 163 |
| 2024 July | 98 | 42 | 140 |
| 2024 June | 88 | 47 | 135 |
| 2024 May | 98 | 37 | 135 |
| 2024 April | 90 | 42 | 132 |
| 2024 March | 62 | 35 | 97 |
| 2024 February | 53 | 42 | 95 |
| 2024 January | 86 | 29 | 115 |
| 2023 December | 52 | 15 | 67 |
| 2023 November | 85 | 28 | 113 |
| 2023 October | 66 | 28 | 94 |
| 2023 September | 101 | 24 | 125 |
| 2023 August | 53 | 16 | 69 |
| 2023 July | 93 | 29 | 122 |
| 2023 June | 90 | 18 | 108 |
| 2023 May | 48 | 23 | 71 |
| 2023 April | 50 | 28 | 78 |
| 2023 March | 61 | 29 | 90 |
| 2023 February | 50 | 30 | 80 |
| 2023 January | 77 | 73 | 150 |
| 2022 December | 147 | 71 | 218 |
| 2022 November | 60 | 48 | 108 |
| 2022 October | 71 | 36 | 107 |
| 2022 September | 74 | 53 | 127 |
| 2022 August | 52 | 53 | 105 |
| 2022 July | 73 | 106 | 179 |
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