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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Apalutamide is an androgen receptor inhibitor approved by the US Food and Drug Administration in 2018 for use against certain prostate cancers&#46; It was approved for use in Europe in March 2021&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> Skin rashes&#44; hypothyroidism&#44; and bone fractures are among apalutamide&#39;s common adverse effects&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Case Descriptions</span><p id="par0010" class="elsevierStylePara elsevierViewall">An 89-year-old man with a history of prostate cancer in treatment with apalutamide for 2 months complained of a skin rash that had first appeared 30 days earlier&#46; The macules and intense peeling started on his chest and spread to involve 80&#37; of his body &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#46; Another 89-year-old man with a history of prostate cancer also consulted us for erythematous papules over large areas of his trunk and limbs&#46; This patient had been in treatment with apalutamide for 1 month and the lesions had appeared 7 days before he consulted us&#46; The rash started on his chest and arms and spread upward and downward&#44; sparing areas not exposed to the sun &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B&#41;&#46; Both patients reported intense itching and general discomfort&#46; The first man was admitted to hospital because his overall condition had declined&#46; In both cases&#44; the biopsies demonstrated a lymphocytic infiltrate in the superficial dermis with significant damage at the dermal-epidermal junction and an abundance of apoptotic keratinocytes&#44; suggesting an adverse drug reaction &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>C and 1D&#41;&#46; The rashes resolved after apalutamide was stopped and a short course of systemic corticosteroids was prescribed&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Discussion</span><p id="par0015" class="elsevierStylePara elsevierViewall">Reports of adverse skin reactions to apalutamide have been scarce in the literature to date&#46; Such reactions are described in the summary of product characteristics for apalutamide and in a report of a series of 68 Japanese patients in clinical trials prior to approval&#59; the adverse skin effects were described ambiguously as rashes&#44; maculopapular rashes&#44; and generalized rashes&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1&#44;2</span></a> Such skin lesions developed at one time or another in 51&#46;7&#37; of the patients on apalutamide&#44; and there was a significant correlation between the presence of rashes and drug plasma concentration&#46; In contrast&#44; no correlation was detected between exposure indicated by plasma concentrations and symptom severity&#44; nor between the incidence of lesions and any patient characteristics at baseline&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> The frequency and severity of rashes in the Japanese series was greater than has been observed in patients in other geographic areas&#46; A case of epidermal necrolysis due to apalutamide has been reported&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Other androgen receptor inhibitors&#44; however&#44; have more often been reported to cause adverse skin reactions&#46; Noteworthy are photosensitivity reactions associated with flutamide and bicalutamide&#44; and case reports of a maculopapular rash and acute generalized exanthematous pustulosis related to enzalutamide&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">4&#44;5</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="par0025" class="elsevierStylePara elsevierViewall">We have presented 2 cases of toxic skin eruptions related to apalutamide&#44; a drug that was recently introduced into our clinical practice&#59; our report shows correlations between histology and symptoms&#46; This drug is expected to be more widely used in the future&#44; and dermatologists should therefore become aware of the characteristics of adverse reactions to it in order to be able to manage both diagnosis and treatment&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conflicts of Interest</span><p id="par0030" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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RF-Adverse Skin Reaction to Apalutamide: An Emerging Effect
FR-Toxicodermia por apalutamida: una entidad emergente
M. Pons Benaventa,
Autor para correspondencia
martiponsbenavent@gmail.com

Corresponding author.
, S. Porcar Sauraa, L. Bou Boludab
a Servicio de Dermatología, Hospital Clínico Universitario de Valencia, Blasco Ibéñez 17, Valencia 46010, Spain
b Servicio de Dermatología, Hospital Arnau de Vilanova, San Clemente 12, Valencia 46015, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Apalutamide is an androgen receptor inhibitor approved by the US Food and Drug Administration in 2018 for use against certain prostate cancers&#46; It was approved for use in Europe in March 2021&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> Skin rashes&#44; hypothyroidism&#44; and bone fractures are among apalutamide&#39;s common adverse effects&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Case Descriptions</span><p id="par0010" class="elsevierStylePara elsevierViewall">An 89-year-old man with a history of prostate cancer in treatment with apalutamide for 2 months complained of a skin rash that had first appeared 30 days earlier&#46; The macules and intense peeling started on his chest and spread to involve 80&#37; of his body &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#46; Another 89-year-old man with a history of prostate cancer also consulted us for erythematous papules over large areas of his trunk and limbs&#46; This patient had been in treatment with apalutamide for 1 month and the lesions had appeared 7 days before he consulted us&#46; The rash started on his chest and arms and spread upward and downward&#44; sparing areas not exposed to the sun &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B&#41;&#46; Both patients reported intense itching and general discomfort&#46; The first man was admitted to hospital because his overall condition had declined&#46; In both cases&#44; the biopsies demonstrated a lymphocytic infiltrate in the superficial dermis with significant damage at the dermal-epidermal junction and an abundance of apoptotic keratinocytes&#44; suggesting an adverse drug reaction &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>C and 1D&#41;&#46; The rashes resolved after apalutamide was stopped and a short course of systemic corticosteroids was prescribed&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Discussion</span><p id="par0015" class="elsevierStylePara elsevierViewall">Reports of adverse skin reactions to apalutamide have been scarce in the literature to date&#46; Such reactions are described in the summary of product characteristics for apalutamide and in a report of a series of 68 Japanese patients in clinical trials prior to approval&#59; the adverse skin effects were described ambiguously as rashes&#44; maculopapular rashes&#44; and generalized rashes&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1&#44;2</span></a> Such skin lesions developed at one time or another in 51&#46;7&#37; of the patients on apalutamide&#44; and there was a significant correlation between the presence of rashes and drug plasma concentration&#46; In contrast&#44; no correlation was detected between exposure indicated by plasma concentrations and symptom severity&#44; nor between the incidence of lesions and any patient characteristics at baseline&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> The frequency and severity of rashes in the Japanese series was greater than has been observed in patients in other geographic areas&#46; A case of epidermal necrolysis due to apalutamide has been reported&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Other androgen receptor inhibitors&#44; however&#44; have more often been reported to cause adverse skin reactions&#46; Noteworthy are photosensitivity reactions associated with flutamide and bicalutamide&#44; and case reports of a maculopapular rash and acute generalized exanthematous pustulosis related to enzalutamide&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">4&#44;5</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="par0025" class="elsevierStylePara elsevierViewall">We have presented 2 cases of toxic skin eruptions related to apalutamide&#44; a drug that was recently introduced into our clinical practice&#59; our report shows correlations between histology and symptoms&#46; This drug is expected to be more widely used in the future&#44; and dermatologists should therefore become aware of the characteristics of adverse reactions to it in order to be able to manage both diagnosis and treatment&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conflicts of Interest</span><p id="par0030" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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