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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Aquagenic wrinkling of the palms was first reported in 1996 by English and McCollough&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Since then&#44; different designations have been used in the literature&#58; Transient Reactive Papulotranslucent Acrokeratoderma&#44;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Aquagenic Syringeal Acrokeratoderma&#44;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> and Aquagenic Palmoplantar Keratoderma&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> It is characterized by thickening of the palms&#44; and on rare occasions also the soles&#44; after brief immersion in water&#46; To date fewer than 50 cases have been reported in the literature&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Although multiple associations have been reported&#44; recent papers highlight the connection with Cystic Fibrosis and Cystic Fibrosis gene &#40;CFTR&#41; mutations&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">In this article the authors describe a patient with aquagenic keratoderma associated with a CFTR mutation&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Case report</span><p id="par0020" class="elsevierStylePara elsevierViewall">An 18-year-old Caucasian female patient presented with a one-month history of pruritus and thickening of palmar skin&#44; shortly after water immersion&#46; Warm water triggered the symptoms more briefly and the dermatosis remitted 20<span class="elsevierStyleHsp" style=""></span>min after water exposure ceased&#46; Her soles were unaffected and she had no other medical complaints&#46; Her personal and family medical histories were irrelevant&#46; On physical examination&#44; palmar skin was unremarkable &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41; but&#44; 5<span class="elsevierStyleHsp" style=""></span>min after water immersion&#44; multiple small&#44; edematous&#44; whitish flat-topped papules were evident&#46; Dermoscopy revealed edematous skin with dilated puncta &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Skin biopsy of palmar papule after water immersion showed orthohyperkeratosis&#44; dermal swelling and dilation of acrosyringia and eccrine ostia &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; Genetic study of the CFTR gene identified a single F508 mutation&#46; No sweat chloride test was performed&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The patient was treated with topical 20&#37; aluminum chloride with improvement of the lesions and complaints&#46; Due to the Cystic Fibrosis carrier state of the patient&#44; she and her family were referred for genetic counseling&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0030" class="elsevierStylePara elsevierViewall">Aquagenic keratoderma is a rare condition characterized by symmetric&#44; flesh-colored to white&#44; edematous&#44; flat-topped papules with dilated ostia located on the palms and finger margins&#46; The soles are rarely involved&#46; The skin lesions typically appear after brief exposure to hot<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> or cold water&#44;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2&#44;5&#44;6</span></a> and usually disappear soon after being dried&#46; When not exposed to water&#44; the skin of affected patients either looks normal or there is hyperlinearity or multiple unremarkable translucent white papules on the palms or soles&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;7</span></a> The condition is usually asymptomatic but it can cause pain&#44; pruritus&#44; burning or tightness&#46; Patients are predominantly female&#44;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;8&#8211;10</span></a> especially among the younger ones &#40;age of onset from 9 to 42 years&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;12</span></a> An autosomal recessive inheritance pattern was initially proposed&#44;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> however more recent cases suggest an autosomal dominant pattern&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> Typically&#44; histological examination &#40;after water exposure&#41; shows hyperkeratosis&#44; orthokeratosis and dilation of acrosyringia and eccrine ostia&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Multiple anecdotal associations have been described in the past&#44; namely&#44; atopy&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> COX-2 inhibitors therapy&#44;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;15</span></a> marasmus&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> palmar hyperhidrosis&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Raynaud&#39;s phenomenon&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> malignant melanoma&#44;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Beh&#231;et disease<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> and nail psoriasis&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> However recent studies tend to emphasize a possible relation between aquagenic keratoderma and cystic fibrosis&#46; It is estimated that more than half the patients with aquagenic keratoderma &#40;56&#46;7&#37;&#41; have documented cystic fibrosis<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#46; Although aquagenic keratoderma seems to be more prevalent in cystic fibrosis patients&#44; Gild et al&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> reported the first case associated with a single mutation in the CFTR gene&#44; suggesting that aquagenic keratoderma may be a sign of the cystic fibrosis carrier state&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The pathogenesis of aquagenic keratoderma remains unknown&#46; Due to the increased sweat chloride concentration in Cystic Fibrosis patients&#44; an increased water-binding capacity of epidermal keratinocytes has been suggested&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#44;19</span></a> Berk et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> however&#44; showed that there was no relationship between sweat chloride concentration and aquagenic wrinkling of the palms score&#46; Several other hypotheses remain in debate&#44; such as eccrine gland<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;21</span></a> or nerve<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> dysfunction&#44; hyperhidrosis&#44;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> defective barrier function of the stratum corneum&#44;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a> occlusion of eccrine duct ostia<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> and weakness of the eccrine duct wall&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Like the patient described&#44; the &#916;F508 is the most commonly reported mutation associated with aquagenic keratoderma in cystic fibrosis patients&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Although this is the most common CFTR mutation &#40;70&#37; of cystic fibrosis mutations in north European Caucasian patients&#41;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;23</span></a> some authors speculate that this particular mutation could represent a predisposing factor for aquagenic keratoderma&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;20</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Multiple effective therapies have been reported&#44; including aluminum chloride&#44;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;17</span></a> antihistamines&#44;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> botulinum toxin injections&#44;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> iontophoresis<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> with variable results&#46; Spontaneous remission has also been described&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3&#44;5&#44;17</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">In the present case&#44; aquagenic keratoderma might represent the sole manifestation of the cystic fibrosis carrier state of the patient&#46; This highlights the importance of considering and testing for this type of genetic abnormality in these patients&#46; Similarly&#44; this type of dermatologic condition should be looked for in both cystic fibrosis patients and known carriers&#44; not only because there are available therapies but also due to the fact that new reports and studies could help clarify the pathogenesis of both conditions&#46; The authors believe that aquagenic keratoderma is an under-diagnosed condition&#44; which can be misdiagnosed as a physiologic whitish discoloration and wrinkling of the palms&#44; a consequence of digit pulp vasoconstriction&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> normally associated with prolonged water exposure&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Ethical disclosures</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Protection of human and animal subjects</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Confidentiality of data</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data and that all the patients included in the study received sufficient information and gave their written informed consent to participate in the study&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Right to privacy and informed consent</span><p id="par0070" class="elsevierStylePara elsevierViewall">The authors have obtained the written informed consent of the patients or subjects mentioned in the article&#46; The corresponding author is in possession of this document&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of interest</span><p id="par0075" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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            0 => "Acroqueratodermia aquag&#233;nica"
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        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Reported for the first time in 1996&#44; aquagenic keratoderma is a rare condition which is characterized by edematous flat-topped papules appearing on palmar skin after water immersion&#46; Multiple anecdotal associations have been described but&#44; recently&#44; the association with cystic fibrosis gene mutations &#40;CFTR&#41; has been highlighted&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The authors describe an 18-year-old female&#44; with one-month complaints of pruritus and swelling of palmar skin after water immersion&#46; On examination&#44; palmar skin was unremarkable but&#44; 5<span class="elsevierStyleHsp" style=""></span>min after water immersion&#44; multiple whitish papules became apparent&#46; CFTR genotype study showed a F508del mutation in one allele &#40;nonhomozygous&#41;&#46; She had no other symptoms and no relevant family history&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Aquagenic keratoderma is probably an under-diagnosed entity that might represent a manifestation of CFTR mutations&#44; making carrier state identification and genetic counseling possible&#46;</p>"
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        "resumen" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Descrita em 1996&#44; a acroqueratodermia aquag&#233;nica &#233; uma entidade rara&#44; caracterizada pelo aparecimento de p&#225;pulas edematosas palmares ap&#243;s contacto com &#225;gua&#46; M&#250;ltiplas associa&#231;&#245;es foram enumeradas mas&#44; recentemente&#44; a associa&#231;&#227;o a muta&#231;&#245;es do gene da fibrose qu&#237;stica foi demonstrada&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Descreve-se o caso de uma mulher de 18 anos&#44; saud&#225;vel&#44; com prurido e edema palmar ap&#243;s imers&#227;o em &#225;gua&#46; O exame objetivo inicial n&#227;o mostrava altera&#231;&#245;es mas&#44; 5&#160;min ap&#243;s imers&#227;o em &#225;gua&#44; observavam-se m&#250;ltiplas p&#225;pulas esbranqui&#231;adas palmares&#46; O estudo do gene da fibrose qu&#237;stica &#40;CFTR&#41; revelou uma muta&#231;&#227;o F508del num dos alelos&#46; A doente negava outras queixas ou hist&#243;ria familiar relevante&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A acroqueratodermia aquag&#233;nica &#233; uma entidade provavelmente subdiagnosticada que poder&#225; constituir uma manifesta&#231;&#227;o de muta&#231;&#245;es do gene CFTR&#44; o que possibilitaria a identifica&#231;&#227;o de portadores e aconselhamento gen&#233;tico&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara">Please cite this article as&#58; Coelho-Macias&#44; V&#46; Acroqueratodermia aquag&#233;nica associada a uma muta&#231;&#227;o do gene da fibrose qu&#237;stica&#46; Rev Port Pneumol 2013&#46; <span class="elsevierStyleInterRef" href="doi:10.1016/j.rppneu.2012.10.005">http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1016&#47;j&#46;rppneu&#46;2012&#46;10&#46;005</span>&#46;</p>"
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Palmar skin on initial physical examination&#46;</p>"
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          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; Palmar skin after 5<span class="elsevierStyleHsp" style=""></span>min water immersion&#58; subtle whitish&#44; edematous and flat-topped papules became apparent&#46; &#40;B&#41; Detail on dermoscopy&#46;</p>"
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Case report
Aquagenic keratoderma associated with a mutation of the cystic fibrosis gene
Acroqueratodermia aquagénica associada a uma mutação do gene da fibrose quística
V. Coelho-Macias
Corresponding author
vmcmacias@gmail.com

Corresponding author.
, S. Fernandes, P. Lamarão, F. Assis-Pacheco, J. Cardoso
Serviço de Dermatologia e Venereologia, Hospital de Curry Cabral, Lisboa, Portugal
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Aquagenic wrinkling of the palms was first reported in 1996 by English and McCollough&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Since then&#44; different designations have been used in the literature&#58; Transient Reactive Papulotranslucent Acrokeratoderma&#44;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Aquagenic Syringeal Acrokeratoderma&#44;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> and Aquagenic Palmoplantar Keratoderma&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> It is characterized by thickening of the palms&#44; and on rare occasions also the soles&#44; after brief immersion in water&#46; To date fewer than 50 cases have been reported in the literature&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Although multiple associations have been reported&#44; recent papers highlight the connection with Cystic Fibrosis and Cystic Fibrosis gene &#40;CFTR&#41; mutations&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">In this article the authors describe a patient with aquagenic keratoderma associated with a CFTR mutation&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Case report</span><p id="par0020" class="elsevierStylePara elsevierViewall">An 18-year-old Caucasian female patient presented with a one-month history of pruritus and thickening of palmar skin&#44; shortly after water immersion&#46; Warm water triggered the symptoms more briefly and the dermatosis remitted 20<span class="elsevierStyleHsp" style=""></span>min after water exposure ceased&#46; Her soles were unaffected and she had no other medical complaints&#46; Her personal and family medical histories were irrelevant&#46; On physical examination&#44; palmar skin was unremarkable &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41; but&#44; 5<span class="elsevierStyleHsp" style=""></span>min after water immersion&#44; multiple small&#44; edematous&#44; whitish flat-topped papules were evident&#46; Dermoscopy revealed edematous skin with dilated puncta &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Skin biopsy of palmar papule after water immersion showed orthohyperkeratosis&#44; dermal swelling and dilation of acrosyringia and eccrine ostia &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; Genetic study of the CFTR gene identified a single F508 mutation&#46; No sweat chloride test was performed&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The patient was treated with topical 20&#37; aluminum chloride with improvement of the lesions and complaints&#46; Due to the Cystic Fibrosis carrier state of the patient&#44; she and her family were referred for genetic counseling&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0030" class="elsevierStylePara elsevierViewall">Aquagenic keratoderma is a rare condition characterized by symmetric&#44; flesh-colored to white&#44; edematous&#44; flat-topped papules with dilated ostia located on the palms and finger margins&#46; The soles are rarely involved&#46; The skin lesions typically appear after brief exposure to hot<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> or cold water&#44;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2&#44;5&#44;6</span></a> and usually disappear soon after being dried&#46; When not exposed to water&#44; the skin of affected patients either looks normal or there is hyperlinearity or multiple unremarkable translucent white papules on the palms or soles&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;7</span></a> The condition is usually asymptomatic but it can cause pain&#44; pruritus&#44; burning or tightness&#46; Patients are predominantly female&#44;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;8&#8211;10</span></a> especially among the younger ones &#40;age of onset from 9 to 42 years&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;12</span></a> An autosomal recessive inheritance pattern was initially proposed&#44;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> however more recent cases suggest an autosomal dominant pattern&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> Typically&#44; histological examination &#40;after water exposure&#41; shows hyperkeratosis&#44; orthokeratosis and dilation of acrosyringia and eccrine ostia&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Multiple anecdotal associations have been described in the past&#44; namely&#44; atopy&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> COX-2 inhibitors therapy&#44;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;15</span></a> marasmus&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> palmar hyperhidrosis&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Raynaud&#39;s phenomenon&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> malignant melanoma&#44;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Beh&#231;et disease<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> and nail psoriasis&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> However recent studies tend to emphasize a possible relation between aquagenic keratoderma and cystic fibrosis&#46; It is estimated that more than half the patients with aquagenic keratoderma &#40;56&#46;7&#37;&#41; have documented cystic fibrosis<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#46; Although aquagenic keratoderma seems to be more prevalent in cystic fibrosis patients&#44; Gild et al&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> reported the first case associated with a single mutation in the CFTR gene&#44; suggesting that aquagenic keratoderma may be a sign of the cystic fibrosis carrier state&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The pathogenesis of aquagenic keratoderma remains unknown&#46; Due to the increased sweat chloride concentration in Cystic Fibrosis patients&#44; an increased water-binding capacity of epidermal keratinocytes has been suggested&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#44;19</span></a> Berk et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> however&#44; showed that there was no relationship between sweat chloride concentration and aquagenic wrinkling of the palms score&#46; Several other hypotheses remain in debate&#44; such as eccrine gland<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;21</span></a> or nerve<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> dysfunction&#44; hyperhidrosis&#44;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> defective barrier function of the stratum corneum&#44;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a> occlusion of eccrine duct ostia<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> and weakness of the eccrine duct wall&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Like the patient described&#44; the &#916;F508 is the most commonly reported mutation associated with aquagenic keratoderma in cystic fibrosis patients&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Although this is the most common CFTR mutation &#40;70&#37; of cystic fibrosis mutations in north European Caucasian patients&#41;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;23</span></a> some authors speculate that this particular mutation could represent a predisposing factor for aquagenic keratoderma&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;20</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Multiple effective therapies have been reported&#44; including aluminum chloride&#44;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;17</span></a> antihistamines&#44;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> botulinum toxin injections&#44;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> iontophoresis<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> with variable results&#46; Spontaneous remission has also been described&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3&#44;5&#44;17</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">In the present case&#44; aquagenic keratoderma might represent the sole manifestation of the cystic fibrosis carrier state of the patient&#46; This highlights the importance of considering and testing for this type of genetic abnormality in these patients&#46; Similarly&#44; this type of dermatologic condition should be looked for in both cystic fibrosis patients and known carriers&#44; not only because there are available therapies but also due to the fact that new reports and studies could help clarify the pathogenesis of both conditions&#46; The authors believe that aquagenic keratoderma is an under-diagnosed condition&#44; which can be misdiagnosed as a physiologic whitish discoloration and wrinkling of the palms&#44; a consequence of digit pulp vasoconstriction&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> normally associated with prolonged water exposure&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Ethical disclosures</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Protection of human and animal subjects</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Confidentiality of data</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data and that all the patients included in the study received sufficient information and gave their written informed consent to participate in the study&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Right to privacy and informed consent</span><p id="par0070" class="elsevierStylePara elsevierViewall">The authors have obtained the written informed consent of the patients or subjects mentioned in the article&#46; 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        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Reported for the first time in 1996&#44; aquagenic keratoderma is a rare condition which is characterized by edematous flat-topped papules appearing on palmar skin after water immersion&#46; Multiple anecdotal associations have been described but&#44; recently&#44; the association with cystic fibrosis gene mutations &#40;CFTR&#41; has been highlighted&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The authors describe an 18-year-old female&#44; with one-month complaints of pruritus and swelling of palmar skin after water immersion&#46; On examination&#44; palmar skin was unremarkable but&#44; 5<span class="elsevierStyleHsp" style=""></span>min after water immersion&#44; multiple whitish papules became apparent&#46; CFTR genotype study showed a F508del mutation in one allele &#40;nonhomozygous&#41;&#46; She had no other symptoms and no relevant family history&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Aquagenic keratoderma is probably an under-diagnosed entity that might represent a manifestation of CFTR mutations&#44; making carrier state identification and genetic counseling possible&#46;</p>"
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      "pt" => array:2 [
        "titulo" => "Resumo"
        "resumen" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Descrita em 1996&#44; a acroqueratodermia aquag&#233;nica &#233; uma entidade rara&#44; caracterizada pelo aparecimento de p&#225;pulas edematosas palmares ap&#243;s contacto com &#225;gua&#46; M&#250;ltiplas associa&#231;&#245;es foram enumeradas mas&#44; recentemente&#44; a associa&#231;&#227;o a muta&#231;&#245;es do gene da fibrose qu&#237;stica foi demonstrada&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Descreve-se o caso de uma mulher de 18 anos&#44; saud&#225;vel&#44; com prurido e edema palmar ap&#243;s imers&#227;o em &#225;gua&#46; O exame objetivo inicial n&#227;o mostrava altera&#231;&#245;es mas&#44; 5&#160;min ap&#243;s imers&#227;o em &#225;gua&#44; observavam-se m&#250;ltiplas p&#225;pulas esbranqui&#231;adas palmares&#46; O estudo do gene da fibrose qu&#237;stica &#40;CFTR&#41; revelou uma muta&#231;&#227;o F508del num dos alelos&#46; A doente negava outras queixas ou hist&#243;ria familiar relevante&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A acroqueratodermia aquag&#233;nica &#233; uma entidade provavelmente subdiagnosticada que poder&#225; constituir uma manifesta&#231;&#227;o de muta&#231;&#245;es do gene CFTR&#44; o que possibilitaria a identifica&#231;&#227;o de portadores e aconselhamento gen&#233;tico&#46;</p>"
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      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara">Please cite this article as&#58; Coelho-Macias&#44; V&#46; Acroqueratodermia aquag&#233;nica associada a uma muta&#231;&#227;o do gene da fibrose qu&#237;stica&#46; Rev Port Pneumol 2013&#46; <span class="elsevierStyleInterRef" href="doi:10.1016/j.rppneu.2012.10.005">http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1016&#47;j&#46;rppneu&#46;2012&#46;10&#46;005</span>&#46;</p>"
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Palmar skin on initial physical examination&#46;</p>"
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        "etiqueta" => "Figure 2"
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          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; Palmar skin after 5<span class="elsevierStyleHsp" style=""></span>min water immersion&#58; subtle whitish&#44; edematous and flat-topped papules became apparent&#46; &#40;B&#41; Detail on dermoscopy&#46;</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Histopathologic examination of palmar papule after water immersion showing orthohyperkeratosis&#44; dermal swelling and dilated acrosyringia and eccrine ostia&#46;</p>"
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