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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">Actinic keratosis &#40;AK&#41; is a premalignant skin lesion that can progress to squamous cell carcinoma&#46; Ingenol mebutate &#40;IM&#41; gel is a widely used topical treatment for the management of nonhyperkeratotic AK&#46; This gel has also been used off-label to treat actinic cheilitis&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Case Description</span><p id="par0010" class="elsevierStylePara elsevierViewall">An 85-year-old Caucasian man with a history of hypertension and dyslipidemia was referred to our clinic for asymptomatic scaly lesions on the scalp that had appeared 5 years earlier&#46; Physical examination revealed multiple erythematous&#44; scaly plaques &#40;0&#46;5&#8211;1&#160;cm&#41; on the surface of the scalp containing little infiltrate&#46; Because the lesions were clinically compatible with AK the patient was prescribed 0&#46;015&#37; IM gel&#44; to be applied once per day for 3 consecutive days&#46; One week after treatment&#44; the patient developed a painful skin rash consisting of multiple vesicular lesions located predominantly in the left cervical area compatible with herpes zoster &#40;HZ&#41;&#46; The lesion distribution suggested involvement of branches C2&#8211;C4 of the cervical plexus&#46; Polymerase chain reaction &#40;PCR&#41; confirmed a diagnosis of varicella-zoster virus &#40;VZV&#41;&#46; Brivudine &#40;125&#160;mg&#47;d&#41; was prescribed for 7 days&#46; The HZ lesions resolved without complications&#46; Based on the location and timing of the lesions&#44; reactivation of VZV was attributed to treatment with IM&#46; Consequently&#44; the Spanish Pharmacovigilance System for Medicinal Products for Human Use &#40;SEFV-H&#41; was informed about this side effect&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Discussion</span><p id="par0015" class="elsevierStylePara elsevierViewall">Adverse skin reactions to IM include erythema&#44; post-inflammatory hyperpigmentation&#44; and residual scars&#44; all of which are likely related to local inflammation caused by IM&#46; Erosive pustular dermatosis of the scalp&#44;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> bullous reactions&#44;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and squamous cell carcinoma<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> have been associated with IM treatment&#46; To date&#44; no cases of VZV reactivation associated with IM treatment have been described in Europe&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In August 2015&#44; following reports of 20 such cases in the United States in the post-marketing phase&#44; the Food and Drug Administration &#40;FDA&#41; included HZ as a possible adverse effect of IM&#44; and added this information to the summary of product characteristics &#40;SmPC&#41;&#46; However&#44; this adverse effect has not been included in the SmPC for IM in Europe&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The total number of recorded cases is not entirely clear&#44; as some reported cases may have been due to herpes simplex virus &#40;HSV&#41; reactivation&#46; While HSV latency can be mediated by distinct mechanisms&#44; one gene implicated in this process is the latency-associated transcription &#40;LAT&#41; gene&#46; Certain stimuli that inhibit the expression of this gene&#44; including hypoxia and cellular apoptosis induced by IM or other topical treatments for AK&#44; can induce transcription and reactivation of viral genes in certain patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Age and immune compromise are other known risk factors for VZV reactivation&#46; Because patients with AK are generally over 60 years of age&#44; the use of IM in this subgroup of patients could increase the risk of developing HZ&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusion</span><p id="par0035" class="elsevierStylePara elsevierViewall">To date&#44; there have been no other reports in Europe of VZV reactivation in immunocompetent patients treated with IM gel&#46; In cases in which a blistering reaction occurs after IM treatment&#44; we believe it is important to perform a Tzank or PCR test&#44; based on which an association with VZV or HSV can be ruled out&#46; If VZV reactivation is confirmed&#44; antiviral treatment should be started immediately to reduce the risk of late complications that can lead to high morbidity&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conflicts of Interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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RF-Herpes Zoster Triggered by Ingenol Mebutate Gel: First European Case Report
FR-Aparición de herpes zoster secundario a la aplicación de ingenol mebutato en gel: comunicación del primer caso europeo
M. Garayar Canteroa,
Autor para correspondencia
mariagarayar@gmail.com

Corresponding author.
, E. Manrique-Silvab, E. Godoy-Gijónc
a Hospital Clínico Universitario de Valladolid, Valladolid, Spain
b Fundación Instituto Valenciano de Oncología, Valencia, Spain
c Hospital Clínico de Salamanca, Salamanca, Spain
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Physical examination revealed multiple erythematous&#44; scaly plaques &#40;0&#46;5&#8211;1&#160;cm&#41; on the surface of the scalp containing little infiltrate&#46; Because the lesions were clinically compatible with AK the patient was prescribed 0&#46;015&#37; IM gel&#44; to be applied once per day for 3 consecutive days&#46; One week after treatment&#44; the patient developed a painful skin rash consisting of multiple vesicular lesions located predominantly in the left cervical area compatible with herpes zoster &#40;HZ&#41;&#46; The lesion distribution suggested involvement of branches C2&#8211;C4 of the cervical plexus&#46; Polymerase chain reaction &#40;PCR&#41; confirmed a diagnosis of varicella-zoster virus &#40;VZV&#41;&#46; Brivudine &#40;125&#160;mg&#47;d&#41; was prescribed for 7 days&#46; The HZ lesions resolved without complications&#46; Based on the location and timing of the lesions&#44; reactivation of VZV was attributed to treatment with IM&#46; Consequently&#44; the Spanish Pharmacovigilance System for Medicinal Products for Human Use &#40;SEFV-H&#41; was informed about this side effect&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Discussion</span><p id="par0015" class="elsevierStylePara elsevierViewall">Adverse skin reactions to IM include erythema&#44; post-inflammatory hyperpigmentation&#44; and residual scars&#44; all of which are likely related to local inflammation caused by IM&#46; Erosive pustular dermatosis of the scalp&#44;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> bullous reactions&#44;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and squamous cell carcinoma<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> have been associated with IM treatment&#46; To date&#44; no cases of VZV reactivation associated with IM treatment have been described in Europe&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In August 2015&#44; following reports of 20 such cases in the United States in the post-marketing phase&#44; the Food and Drug Administration &#40;FDA&#41; included HZ as a possible adverse effect of IM&#44; and added this information to the summary of product characteristics &#40;SmPC&#41;&#46; However&#44; this adverse effect has not been included in the SmPC for IM in Europe&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The total number of recorded cases is not entirely clear&#44; as some reported cases may have been due to herpes simplex virus &#40;HSV&#41; reactivation&#46; While HSV latency can be mediated by distinct mechanisms&#44; one gene implicated in this process is the latency-associated transcription &#40;LAT&#41; gene&#46; Certain stimuli that inhibit the expression of this gene&#44; including hypoxia and cellular apoptosis induced by IM or other topical treatments for AK&#44; can induce transcription and reactivation of viral genes in certain patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Age and immune compromise are other known risk factors for VZV reactivation&#46; Because patients with AK are generally over 60 years of age&#44; the use of IM in this subgroup of patients could increase the risk of developing HZ&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusion</span><p id="par0035" class="elsevierStylePara elsevierViewall">To date&#44; there have been no other reports in Europe of VZV reactivation in immunocompetent patients treated with IM gel&#46; In cases in which a blistering reaction occurs after IM treatment&#44; we believe it is important to perform a Tzank or PCR test&#44; based on which an association with VZV or HSV can be ruled out&#46; If VZV reactivation is confirmed&#44; antiviral treatment should be started immediately to reduce the risk of late complications that can lead to high morbidity&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conflicts of Interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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