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2</a>&#41;&#46; The patient was treated with acitretin 25<span class="elsevierStyleHsp" style=""></span>mg daily and after six months of treatment a remarkable clinical and dermatoscopic improvement was achieved in the skin lesions of the face &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41; and a good response in the legs &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46;</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="sect0025">Discussion</span><p id="par0010" class="elsevierStylePara elsevierViewall">Darier disease &#40;DD&#41; or Darier-White disease is an autosomal dominant inherited keratinization disorder&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> It has complete penetrance but variable expression with a negative impact on life quality&#46; First described by Jean Darier and James Clarke White in 1889&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> It is caused by a mutation in the ATP2A2 gene &#8210; in all cases &#8210; which encodes the sarco&#47;endoplasmic reticulum Ca2&#43;ATPase type 2 &#40;SERCA2&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The prevalence ranges from 1&#47;30&#44;000 to 1&#47;50&#44;000&#44; and affects both genders in equal proportion&#44; without ethnic differences&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The classical clinical findings are hyperkeratotic papules in a seborrheic distribution involving the trunk&#44; scalp&#44; face&#44; and lateral aspects of the neck&#46; They are usually symmetric lesions&#44; but mosaic Darier disease can occur if lesions follow Blaschko&#39;s lines unilaterally or if they are distributed in focal areas of increased severity superimposed on a background of generalized DD&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The latter corresponds to the present case&#44; where unilateral facial lesions were found&#46; Other features include maceration of intertriginous areas&#44; palmar pits&#44; and whitish papules in the oral mucosa &#40;hard palate&#41;&#46; Nail abnormalities can be found showing&#59; V&#8209;shaped notches at the distal edge of the nail&#44; longitudinal white and red alternating streaks&#44; subungual hyperkeratosis&#44; splinter hemorrhages&#44; and nail fragility&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The main histopathologic findings are acantholysis due to loss of cell adhesion and dyskeratotic keratinocytes &#40;premature cells&#41;&#46; These dyskeratotic cells are described as &#8220;corp ronds&#8221; in the spinous-granular layer and &#8220;grains&#8221; in the stratum corneum&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Dermatoscopic features have also been described in DD&#46; They include comedo-like openings with a central polygonal or star-like yellowish&#47;brownish structure&#44; surrounded by a whitish halo&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a> A pink homogeneous structureless background is associated with white scales and dotted or linear vessels&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> First-line treatment in DD includes topical or systemic retinoids&#44; becoming acitretin a valuable alternative since 1988&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Only five reports have been published describing DD dermatoscopic findings&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5&#44;7&#44;8</span></a> In this case&#44; the authors have been able to compare the results of acitretin treatment &#8210; before and after &#8210; using dermatoscopy&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Acitretin is the active metabolite of etretinate&#46; It was introduced in 1988 and replaced etretinate&#44; mostly due to a better pharmacokinetic profile and lesser adverse effects&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Acitretin strongly binds to cellular retinoic acid-binding protein&#44; which transports retinoic acid from the cytosol to the nucleus&#46; It modifies the transcription of over 500 genes&#44; reduces proliferation&#44; and increases keratinocyte differentiation&#46; It inhibits induction of T-helper-17 &#40;Th-17&#41; cells by suppressing Interleukin-6 &#40;IL-6&#41; and promotes differentiation of T regulatory cells&#46; Acitretin reduces keratinocyte production of vascular endothelial growth factors and inhibits neutrophil migration&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> In summary&#44; it modulates keratinocytes proliferation and differentiation and has immunomodulatory and anti-inflammatory activities&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Therefore&#44; acitretin has been shown to have a consistent therapeutic efficacy in disorders of keratinization &#40;e&#46;g&#46;&#44; bullous ichtyosiform erythroderma&#44; lamellar ichtyosis&#44; pityriasis rubra pilaris&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> It has become the first choice for the treatment of Darier Disease&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In the present study&#8217;s case&#44; the effect of acitretin was remarkable but the most important aspect was to demonstrate the effectiveness of this drug using dermatoscopic follow-up&#46; Before treatment&#44; the patient had big comedo-like openings &#40;measuring 300 to 500 microns as is shown in the dermatoscope scale&#41; with a central hyperkeratotic yellowish&#47;brownish structure&#44; surrounded by a whitish halo &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>A&#41;&#46; After 6-months of treatment these lesions involuted almost completely&#44; leaving a few white shiny structures that could only be seen under dermoscopy as a result of the inflammatory and fibrotic process that followed the treatment with acitretin &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>B&#44; <a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>B&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">We confirmed the importance of dermatoscopy as a useful diagnostic tool for clinical diagnosis in dermatology&#46; In this case&#44; dermatoscopy was also essential for monitoring the treatment of the patient with DD&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Financial support</span><p id="par0045" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Authors&#39; contributions</span><p id="par0050" class="elsevierStylePara elsevierViewall">Catalina Silva-Hirschberg&#58; Approval of the final version of the manuscript&#59; critical literature review&#59; manuscript critical review&#59; preparation and writing of the manuscript&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Ra&#250;l Cabrera&#58; Approval of the final version of the manuscript&#59; intellectual participation in propaedeutic and&#47;or therapeutic management of studied cases&#59; manuscript critical review&#59; preparation and writing of the manuscript&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Mar&#237;a Paz Roll&#225;n&#58; Approval of the final version of the manuscript&#59; critical literature review&#59; manuscript critical review&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Alex Castro&#58; Approval of the final version of the manuscript&#59; intellectual participation in propaedeutic and&#47;or therapeutic management of studied cases&#59; manuscript critical review&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conflicts of interest</span><p id="par0070" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Darier disease is an uncommon autosomal dominant inherited disease&#44; caused by a mutation in the <span class="elsevierStyleItalic">ATP2A2</span> gene&#46; The clinical findings are hyperkeratotic papules on the trunk&#44; scalp&#44; face&#44; and neck&#44; maceration of intertriginous areas&#44; palmar pits&#44; whitish papules on the oral mucosa and nail abnormalities&#46; The main histopathologic findings are acantholysis and dyskeratotic keratinocytes&#46; Dermatoscopic features are comedo-like openings with a central polygonal yellowish&#47;brownish structure&#44; surrounded by a whitish halo&#46; First-line treatment includes acitretin&#46; Five reports have been published describing Darier disease dermatoscopic findings&#46; Herein&#44; we report for the first time a patient under acitretin treatment and dermatoscopic follow-up&#46;</p></span>"
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Images in Dermatology
Darier disease: the use of dermoscopy in monitoring acitretin treatment
Catalina Silva-Hirschberga,
Corresponding author
casilvah@udd.cl

Corresponding author.
, Raúl Cabreraa, María Paz Rollána, Alex Castrob
a Department of Dermatology, Facultad de Medicina, Clínica Alemana, Universidad del Desarrollo, Santiago, Chile
b Department of Pathology, Facultad de Medicina, Clínica Alemana, Universidad del Desarrollo, Santiago, Chile
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2</a>&#41;&#46; The patient was treated with acitretin 25<span class="elsevierStyleHsp" style=""></span>mg daily and after six months of treatment a remarkable clinical and dermatoscopic improvement was achieved in the skin lesions of the face &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41; and a good response in the legs &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46;</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="sect0025">Discussion</span><p id="par0010" class="elsevierStylePara elsevierViewall">Darier disease &#40;DD&#41; or Darier-White disease is an autosomal dominant inherited keratinization disorder&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> It has complete penetrance but variable expression with a negative impact on life quality&#46; First described by Jean Darier and James Clarke White in 1889&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> It is caused by a mutation in the ATP2A2 gene &#8210; in all cases &#8210; which encodes the sarco&#47;endoplasmic reticulum Ca2&#43;ATPase type 2 &#40;SERCA2&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The prevalence ranges from 1&#47;30&#44;000 to 1&#47;50&#44;000&#44; and affects both genders in equal proportion&#44; without ethnic differences&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The classical clinical findings are hyperkeratotic papules in a seborrheic distribution involving the trunk&#44; scalp&#44; face&#44; and lateral aspects of the neck&#46; They are usually symmetric lesions&#44; but mosaic Darier disease can occur if lesions follow Blaschko&#39;s lines unilaterally or if they are distributed in focal areas of increased severity superimposed on a background of generalized DD&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The latter corresponds to the present case&#44; where unilateral facial lesions were found&#46; Other features include maceration of intertriginous areas&#44; palmar pits&#44; and whitish papules in the oral mucosa &#40;hard palate&#41;&#46; Nail abnormalities can be found showing&#59; V&#8209;shaped notches at the distal edge of the nail&#44; longitudinal white and red alternating streaks&#44; subungual hyperkeratosis&#44; splinter hemorrhages&#44; and nail fragility&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The main histopathologic findings are acantholysis due to loss of cell adhesion and dyskeratotic keratinocytes &#40;premature cells&#41;&#46; These dyskeratotic cells are described as &#8220;corp ronds&#8221; in the spinous-granular layer and &#8220;grains&#8221; in the stratum corneum&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Dermatoscopic features have also been described in DD&#46; They include comedo-like openings with a central polygonal or star-like yellowish&#47;brownish structure&#44; surrounded by a whitish halo&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a> A pink homogeneous structureless background is associated with white scales and dotted or linear vessels&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> First-line treatment in DD includes topical or systemic retinoids&#44; becoming acitretin a valuable alternative since 1988&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Only five reports have been published describing DD dermatoscopic findings&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5&#44;7&#44;8</span></a> In this case&#44; the authors have been able to compare the results of acitretin treatment &#8210; before and after &#8210; using dermatoscopy&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Acitretin is the active metabolite of etretinate&#46; It was introduced in 1988 and replaced etretinate&#44; mostly due to a better pharmacokinetic profile and lesser adverse effects&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Acitretin strongly binds to cellular retinoic acid-binding protein&#44; which transports retinoic acid from the cytosol to the nucleus&#46; It modifies the transcription of over 500 genes&#44; reduces proliferation&#44; and increases keratinocyte differentiation&#46; It inhibits induction of T-helper-17 &#40;Th-17&#41; cells by suppressing Interleukin-6 &#40;IL-6&#41; and promotes differentiation of T regulatory cells&#46; Acitretin reduces keratinocyte production of vascular endothelial growth factors and inhibits neutrophil migration&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> In summary&#44; it modulates keratinocytes proliferation and differentiation and has immunomodulatory and anti-inflammatory activities&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Therefore&#44; acitretin has been shown to have a consistent therapeutic efficacy in disorders of keratinization &#40;e&#46;g&#46;&#44; bullous ichtyosiform erythroderma&#44; lamellar ichtyosis&#44; pityriasis rubra pilaris&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> It has become the first choice for the treatment of Darier Disease&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In the present study&#8217;s case&#44; the effect of acitretin was remarkable but the most important aspect was to demonstrate the effectiveness of this drug using dermatoscopic follow-up&#46; Before treatment&#44; the patient had big comedo-like openings &#40;measuring 300 to 500 microns as is shown in the dermatoscope scale&#41; with a central hyperkeratotic yellowish&#47;brownish structure&#44; surrounded by a whitish halo &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>A&#41;&#46; After 6-months of treatment these lesions involuted almost completely&#44; leaving a few white shiny structures that could only be seen under dermoscopy as a result of the inflammatory and fibrotic process that followed the treatment with acitretin &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>B&#44; <a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>B&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">We confirmed the importance of dermatoscopy as a useful diagnostic tool for clinical diagnosis in dermatology&#46; In this case&#44; dermatoscopy was also essential for monitoring the treatment of the patient with DD&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Financial support</span><p id="par0045" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Authors&#39; contributions</span><p id="par0050" class="elsevierStylePara elsevierViewall">Catalina Silva-Hirschberg&#58; Approval of the final version of the manuscript&#59; critical literature review&#59; manuscript critical review&#59; preparation and writing of the manuscript&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Ra&#250;l Cabrera&#58; Approval of the final version of the manuscript&#59; intellectual participation in propaedeutic and&#47;or therapeutic management of studied cases&#59; manuscript critical review&#59; preparation and writing of the manuscript&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Mar&#237;a Paz Roll&#225;n&#58; Approval of the final version of the manuscript&#59; critical literature review&#59; manuscript critical review&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Alex Castro&#58; Approval of the final version of the manuscript&#59; intellectual participation in propaedeutic and&#47;or therapeutic management of studied cases&#59; manuscript critical review&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conflicts of interest</span><p id="par0070" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Darier disease is an uncommon autosomal dominant inherited disease&#44; caused by a mutation in the <span class="elsevierStyleItalic">ATP2A2</span> gene&#46; The clinical findings are hyperkeratotic papules on the trunk&#44; scalp&#44; face&#44; and neck&#44; maceration of intertriginous areas&#44; palmar pits&#44; whitish papules on the oral mucosa and nail abnormalities&#46; The main histopathologic findings are acantholysis and dyskeratotic keratinocytes&#46; Dermatoscopic features are comedo-like openings with a central polygonal yellowish&#47;brownish structure&#44; surrounded by a whitish halo&#46; First-line treatment includes acitretin&#46; Five reports have been published describing Darier disease dermatoscopic findings&#46; Herein&#44; we report for the first time a patient under acitretin treatment and dermatoscopic follow-up&#46;</p></span>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Light microscopy shows hyperkeratosis&#44; suprabasal clefting&#44; and dyskeratotic cells&#46; There is a mild lymphocytic infiltrate in the papillary dermis &#40;Hematoxylin &#38; eosin&#44; &#215;100&#41;&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Dermatoscopic examination &#40;&#215;10&#41;&#46; &#40;A&#41;&#44; Before acitretin treatment&#46; Big comedo-like openings &#40;300 to 500 microns&#41; with a central hyperkeratotic structure&#44; surrounded by a whitish scaling halo&#46; &#40;B&#41;&#44; After acitretin treatment&#46; Few white shiny clods with a pinkish homogeneous background&#46;</p>"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Dermatoscopic examination &#40;&#215;10&#41;&#46; &#40;A&#41;&#44; Before acitretin treatment&#44; multiple confluent big comedo-like openings with a central hyperkeratotic structure surrounded by a whitish scaling halo are seen in the legs&#46; &#40;B&#41;&#44; After acitretin treatment&#44; white shiny clods &#40;of different size&#41; and crust are found in the skin&#46;</p>"
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Article information
ISSN: 03650596
Original language: English
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