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1</a>&#41;&#46; The patch had developed over a few days&#44; persisted since&#44; and no other lesions were found upon complete mucocutaneous examination&#46; Under dermoscopy&#44; white streaks on a violaceus background could be observed &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; The patient had a past personal history of metastatic melanoma under treatment with nivolumab 240&#8239;mg every two weeks until the date&#46; She started it 20 months prior to the appearance of the umbilical patch&#46; A 4&#8239;mm punch biopsy was performed&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Histology showed hyperkeratosis and cytoid bodies with a bandlike inflammatory cell infiltrate composed of lymphocytes&#44; histiocytes&#44; and occasional eosinophils in the papillary dermis &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; The features favored a diagnosis of LP&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Serologies for VHB and VHC were negative&#46; She has been prescribed clobetasol propionate 0&#46;05&#37; ointment for 4 weeks with partial response&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">PD1 pathway inhibits T-cell activation keeping normal immune response balanced&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> Several malignant cells activate PD1 favoring immune escape&#46; Anti-PD1 therapy seeks to activate the immune system in order to kill malignant cells&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> On the other hand&#44; T-cells play an important role in the pathogenesis of LP&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Under this scope&#44; a T-cell activation induced by immunotherapeutic agents blocking PD1 could possibly contribute&#44; along with other stimulating factors&#44; to LP development&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a> Lichenoid skin reactions are well-known side effects of anti-PD1 therapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2&#44;4</span></a> The incidence of related lichenoid eruption is probably underestimated due to its sporadic publication&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> Clinically&#44; it is normally presented as multiple&#44; discrete&#44; erythematous&#44; violaceous papules and plaques&#44;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> thus the patient&#39;s umbilical exclusive location seems a rarity&#46; In fact&#44; the authors have only found one case of LP affecting this area&#44; but not exclusively&#44; in one patient suffering from vitiligo as well&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Interestingly&#44; relatively uncommon forms of other skin conditions exacerbated by anti-PD1 therapy have been described&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2&#44;4</span></a> Although normally presented in the first months after treatment&#44; some authors suggested that the onset of lichenoid eruptions may be delayed compared with other skin reactions&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Indeed&#44; Wang et al&#46; reported that cutaneous adverse reactions may present with delayed onsets and even after discontinuation of therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> However&#44; the authors are aware that another unknown stimulating factor different from nivolumab could not be completely ruled out&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">In conclusion&#44; the authors present a unique case of LP due to the exclusive umbilical location in a patient treated with nivolumab to highlight the potential delayed and alternative clinical presentation of anti-PD1 reactions and that specialized dermatologist consultation should be considered mandatory for accurate diagnosis and best treatment&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financial support</span><p id="par0030" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authors&#8217; contributions</span><p id="par0035" class="elsevierStylePara elsevierViewall">Luisa Martos-Cabrera&#58; Have made substantial contributions to conception and design&#44; or acquisition of data&#44; or analysis and interpretation of data&#59; and have been involved in drafting the manuscript or revising it critically for important intellectual content&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">I&#241;igo Llad&#243;&#58; 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Letter - Clinical
Umbilical lichen planus induced by nivolumab
Luisa Martos-Cabreraa, Iñigo Lladóa, Paloma Fernández-Ricob, Beatriz Butrón-Brisa, Pedro Rodríguez-Jiméneza,
Autor para correspondência
a Department of Dermatology, Hospital Universitario de la Princesa, Madrid, Spain
b Department of Pathology, Hospital Universitario de la Princesa, Madrid, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Skin adverse events are the most common side effects under anti-PD1 immunotherapy&#46; They usually develop early in the course of treatment and do not require interruption&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> However&#44; alternative clinical presentations may be observed&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> The authors encourage you to report them as they may improve knowledge of both&#44; drugs and disease&#46; Hence&#44; the authors present an unusual case of lichen planus &#40;LP&#41; in the umbilicus after the fifteenth dose of nivolumab&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 77-year-old Caucasian female presented with a 3-month history of a red&#44; scaly&#44; itchy&#44; asymmetrical patch located at the umbilicus &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The patch had developed over a few days&#44; persisted since&#44; and no other lesions were found upon complete mucocutaneous examination&#46; Under dermoscopy&#44; white streaks on a violaceus background could be observed &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; The patient had a past personal history of metastatic melanoma under treatment with nivolumab 240&#8239;mg every two weeks until the date&#46; She started it 20 months prior to the appearance of the umbilical patch&#46; A 4&#8239;mm punch biopsy was performed&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Histology showed hyperkeratosis and cytoid bodies with a bandlike inflammatory cell infiltrate composed of lymphocytes&#44; histiocytes&#44; and occasional eosinophils in the papillary dermis &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; The features favored a diagnosis of LP&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Serologies for VHB and VHC were negative&#46; She has been prescribed clobetasol propionate 0&#46;05&#37; ointment for 4 weeks with partial response&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">PD1 pathway inhibits T-cell activation keeping normal immune response balanced&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> Several malignant cells activate PD1 favoring immune escape&#46; Anti-PD1 therapy seeks to activate the immune system in order to kill malignant cells&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> On the other hand&#44; T-cells play an important role in the pathogenesis of LP&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Under this scope&#44; a T-cell activation induced by immunotherapeutic agents blocking PD1 could possibly contribute&#44; along with other stimulating factors&#44; to LP development&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a> Lichenoid skin reactions are well-known side effects of anti-PD1 therapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2&#44;4</span></a> The incidence of related lichenoid eruption is probably underestimated due to its sporadic publication&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> Clinically&#44; it is normally presented as multiple&#44; discrete&#44; erythematous&#44; violaceous papules and plaques&#44;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> thus the patient&#39;s umbilical exclusive location seems a rarity&#46; In fact&#44; the authors have only found one case of LP affecting this area&#44; but not exclusively&#44; in one patient suffering from vitiligo as well&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Interestingly&#44; relatively uncommon forms of other skin conditions exacerbated by anti-PD1 therapy have been described&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2&#44;4</span></a> Although normally presented in the first months after treatment&#44; some authors suggested that the onset of lichenoid eruptions may be delayed compared with other skin reactions&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Indeed&#44; Wang et al&#46; reported that cutaneous adverse reactions may present with delayed onsets and even after discontinuation of therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> However&#44; the authors are aware that another unknown stimulating factor different from nivolumab could not be completely ruled out&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">In conclusion&#44; the authors present a unique case of LP due to the exclusive umbilical location in a patient treated with nivolumab to highlight the potential delayed and alternative clinical presentation of anti-PD1 reactions and that specialized dermatologist consultation should be considered mandatory for accurate diagnosis and best treatment&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financial support</span><p id="par0030" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authors&#8217; contributions</span><p id="par0035" class="elsevierStylePara elsevierViewall">Luisa Martos-Cabrera&#58; Have made substantial contributions to conception and design&#44; or acquisition of data&#44; or analysis and interpretation of data&#59; and have been involved in drafting the manuscript or revising it critically for important intellectual content&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">I&#241;igo Llad&#243;&#58; Have made substantial contributions to conception and design&#44; or acquisition of data&#44; or analysis and interpretation of data&#59; and have been involved in drafting the manuscript or revising it critically for important intellectual content&#59; have made substantial contributions to acquisition of data and have been involved in given final approval of the version to be published&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Paloma Fern&#225;ndez-Rico&#58; Have made substantial contributions to conception and design&#44; acquisition of data and analysis and interpretation of data&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Beatriz Butr&#243;n-Bris&#58; Have made substantial contributions to conception and design&#44; acquisition of data and analysis and interpretation of data&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Pedro Rodr&#237;guez-Jim&#233;nez&#58; Have made substantial contributions to conception and design&#44; or acquisition of data&#44; or analysis and interpretation of data&#59; and have been involved in drafting the manuscript or revising it critically for important intellectual content&#59; given final approval of the version to be published&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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ISSN: 03650596
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