Case for Diagnosis
Hyperkeratosis and Scaling in Identical Twins
Gemelas con cuadro de hiperqueratosis y descamación
C. Medina-Gil
, A.J. Gómez-Duaso, G. Carretero-Hernández
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Servicio de Dermatología, Hospital Universitario de Gran Canaria Dr. Negrín, Gran Canaria, Spain
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Medina-Gil, A.J. Gómez-Duaso, G. Carretero-Hernández" "autores" => array:3 [ 0 => array:4 [ "nombre" => "C." "apellidos" => "Medina-Gil" "email" => array:1 [ 0 => "karol_mg@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "A.J." "apellidos" => "Gómez-Duaso" ] 2 => array:2 [ "nombre" => "G." "apellidos" => "Carretero-Hernández" ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Servicio de Dermatología, Hospital Universitario de Gran Canaria Dr. Negrín, Gran Canaria, Spain" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Gemelas con cuadro de hiperqueratosis y descamación" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:6 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1223 "Ancho" => 917 "Tamanyo" => 285575 ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Medical History</span><p id="par0005" class="elsevierStylePara elsevierViewall">The patients were phenotypically identical twin girls who were born healthy following a normal delivery. Neither the parents nor the other 3 siblings of the girls had any relevant medical history. The twins were brought to our unit at age 2 years for assessment of hyperkeratotic lesions on the hands, feet, and periarticular areas; there were no abnormalities of the mucosas or skin appendages. The patients’ mother reported that the lesions had first appeared when the girls were 2 months of age and had progressed slowly.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Physical Examination</span><p id="par0010" class="elsevierStylePara elsevierViewall">Both girls presented the same clinical picture: thickening and hyperpigmentation of the skin on the hands and feet in a glove-and-stocking distribution as well as in periarticular areas, with superficial scaling in large sheets in some areas. There was also a local increase in fine vellus hair on the limbs (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>, A and B; <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>, A and B).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Histopathology</span><p id="par0015" class="elsevierStylePara elsevierViewall">Skin biopsy revealed a mild perivascular inflammatory infiltrate in the upper dermis. The epidermis exhibited eosinophilic orthokeratotic hyperkeratosis with irregular epidermal acanthosis. The stratum granulosum presented intense vacuolization of keratinocytes, loss of intercellular junctions, and epidermal detachment. Large, irregular aggregates of anomalous keratohyalin granules were also observed (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Additional Tests</span><p id="par0020" class="elsevierStylePara elsevierViewall">Sequencing of the gene <span class="elsevierStyleItalic">KRT2</span> (chromosome 12q) revealed a mutation that causes an amino acid change in the protein encoded by this gene.</p><p id="par0025" class="elsevierStylePara elsevierViewall">What Is Your Diagnosis?</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Diagnosis</span><p id="par0030" class="elsevierStylePara elsevierViewall">Ichthyosis bullosa of Siemens (IBS).</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Clinical Course and Treatment</span><p id="par0035" class="elsevierStylePara elsevierViewall">Both patients presented a good response to topical emollient treatment and topical tazarotene (0.03%), and improvement was seen in the treated areas.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Comment</span><p id="par0040" class="elsevierStylePara elsevierViewall">IBS is a rare, autosomal dominant disorder that was first described by Siemens<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> in 1937. There were no further reports of the condition until 1986, when Traupe et al.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> described a second family affected by the disorder. The underlying genetic alteration in IBS—a mutation in the gene encoding keratin 2e (<span class="elsevierStyleItalic">KRT2e</span>)—was identified in 1994.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Macroscopically, IBS manifests in periarticular areas (knees, ankles, wrists, and elbows) as areas of superficial epidermal shedding (denuded, apparently healthy skin) surrounded by areas of hyperkeratosis, a sign known as the Mauserung phenomenon.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> This term, coined by Siemens, refers to a distinctive characteristic that is of clinical importance because it is not found in other forms of ichthyosis. Mutations in <span class="elsevierStyleItalic">KRT2e</span> are also expressed in the skin of the palms and soles, but, for reasons unknown, do not cause lesions in those areas.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Mutations in <span class="elsevierStyleItalic">KRT2e</span> are expressed in the stratum granulosum and upper stratum spinosum, where they create a pattern known as epidermolytic hyperkeratosis, characterized microscopically by compact hyperkeratosis and vacuolar degeneration of keratinocytes with alteration of keratohyalin granules. This pattern is not pathognomonic, as it can also be found in other entities such as palmoplantar keratoderma (Vörner type) or epidermolytic acanthoma. Incidental foci of epidermolytic hyperkeratosis can even arise in healthy skin. The main clinical and histologic differential diagnosis of IBS is bullous congenital ichthyosiform erythroderma (CIE), and the 2 conditions are easily confused. Bullous CIE is caused by mutations in the genes encoding keratin 1 or keratin 10, which are expressed deeper in the epidermis, in the suprabasal stratum spinosum. Whereas children with IBS are born healthy, children with bullous CIE are born with erythroderma and present a more severe clinical manifestations, including blister formation, extensive desquamation, and fluid and electrolyte abnormalities.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> A definitive diagnosis of IBS is established by means of genetic testing. Our patients, being monozygotic twins, share the same genetic profile; therefore, they both carry the same mutation. Genetic testing was not performed on the girls’ parents or siblings, as none of them presented phenotypic alterations. Because IBS has an autosomal dominant pattern of inheritance, we hypothesize that our patients developed the disorder as a result of a spontaneous mutation that occurred in the zygote before its initial division. This hypothesis would explain how the mutation was transmitted to both girls. The treatment of IBS is fundamentally supportive, and includes topical emollients and keratolytics. One of the most common complications of this disorder is the development of a secondary infection leading to pustulosis, which requires treatment with topical or systemic antibiotics. IBS is a relatively benign disorder whose clinical manifestations tend to stabilize and improve over time.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of Interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Medical History" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Physical Examination" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Histopathology" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "Additional Tests" ] 4 => array:2 [ "identificador" => "sec0025" "titulo" => "Diagnosis" ] 5 => array:2 [ "identificador" => "sec0030" "titulo" => "Clinical Course and Treatment" ] 6 => array:2 [ "identificador" => "sec0035" "titulo" => "Comment" ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflicts of Interest" ] 8 => array:2 [ "identificador" => "xack35263" "titulo" => "Acknowledgments" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara"><span class="elsevierStyleBold">Please cite this article as</span>: Medina-Gil C, et al. Gemelas con cuadro de hiperqueratosis y descamación. Actas Dermosifiliogr. 2012;103:925–6.</p>" ] ] "multimedia" => array:3 [ 0 => array:6 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 872 "Ancho" => 1167 "Tamanyo" => 133402 ] ] ] 1 => array:6 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 737 "Ancho" => 1167 "Tamanyo" => 102350 ] ] ] 2 => array:6 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1223 "Ancho" => 917 "Tamanyo" => 285575 ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dichtung und wahrheit über die ichthyosis bullosa mit bemerkungen zur systematik der epidermolysen" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "H.W. 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Pittelkow" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ng0894-485" "Revista" => array:6 [ "tituloSerie" => "Nat Genet" "fecha" => "1994" "volumen" => "7" "paginaInicial" => "485" "paginaFinal" => "490" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7524919" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ichthyosis bullosa of Siemens: report of a family with evidence of a keratin 2e mutation, and a review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Basarab" 1 => "F.J.D. Smith" 2 => "V.M.L. Jolliffe" 3 => "W.H.I. McLean" 4 => "S. Neill" 5 => "M.H.A. Rustin" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Br J Dermatol" "fecha" => "1999" "volumen" => "140" "paginaInicial" => "689" "paginaFinal" => "695" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10233323" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Revised nomenclature and classification of inherited ichthyoses: Results of the First Ichthyosis Consensus Conference in Sorèze 2009" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V. Oji" 1 => "G. Tadini" 2 => "M. Akiyama" 3 => "C. Blanchet Bardon" 4 => "C. Bodemer" 5 => "E. Bourrat" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaad.2009.11.020" "Revista" => array:6 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "2010" "volumen" => "63" "paginaInicial" => "607" "paginaFinal" => "641" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20643494" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:3 [ "identificador" => "xack35263" "titulo" => "Acknowledgments" "texto" => "<p id="par0055" class="elsevierStylePara elsevierViewall">We would like to thank Dr. Antonio Torrelo for his helpful contributions to the diagnosis.</p>" ] ] ] "idiomaDefecto" => "en" "url" => "/15782190/0000010300000010/v1_201304241352/S1578219012003137/v1_201304241352/en/main.assets" "Apartado" => array:4 [ "identificador" => "6154" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Case for Diagnosis" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15782190/0000010300000010/v1_201304241352/S1578219012003137/v1_201304241352/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219012003137?idApp=UINPBA000044" ]
| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 12 | 13 | 25 |
| 2024 Octubre | 75 | 47 | 122 |
| 2024 Septiembre | 71 | 43 | 114 |
| 2024 Agosto | 103 | 104 | 207 |
| 2024 Julio | 94 | 52 | 146 |
| 2024 Junio | 109 | 68 | 177 |
| 2024 Mayo | 68 | 53 | 121 |
| 2024 Abril | 84 | 33 | 117 |
| 2024 Marzo | 81 | 52 | 133 |
| 2024 Febrero | 77 | 32 | 109 |
| 2024 Enero | 69 | 41 | 110 |
| 2023 Diciembre | 55 | 30 | 85 |
| 2023 Noviembre | 59 | 36 | 95 |
| 2023 Octubre | 50 | 29 | 79 |
| 2023 Septiembre | 61 | 34 | 95 |
| 2023 Agosto | 53 | 31 | 84 |
| 2023 Julio | 71 | 50 | 121 |
| 2023 Junio | 52 | 35 | 87 |
| 2023 Mayo | 71 | 42 | 113 |
| 2023 Abril | 47 | 32 | 79 |
| 2023 Marzo | 54 | 31 | 85 |
| 2023 Febrero | 45 | 29 | 74 |
| 2023 Enero | 31 | 37 | 68 |
| 2022 Diciembre | 50 | 48 | 98 |
| 2022 Noviembre | 33 | 21 | 54 |
| 2022 Octubre | 23 | 27 | 50 |
| 2022 Septiembre | 25 | 36 | 61 |
| 2022 Agosto | 22 | 39 | 61 |
| 2022 Julio | 24 | 31 | 55 |
| 2022 Junio | 24 | 20 | 44 |
| 2022 Mayo | 55 | 37 | 92 |
| 2022 Abril | 44 | 39 | 83 |
| 2022 Marzo | 44 | 72 | 116 |
| 2022 Febrero | 37 | 41 | 78 |
| 2022 Enero | 43 | 49 | 92 |
| 2021 Diciembre | 35 | 51 | 86 |
| 2021 Noviembre | 44 | 51 | 95 |
| 2021 Octubre | 41 | 59 | 100 |
| 2021 Septiembre | 31 | 36 | 67 |
| 2021 Agosto | 37 | 33 | 70 |
| 2021 Julio | 21 | 27 | 48 |
| 2021 Junio | 39 | 30 | 69 |
| 2021 Mayo | 34 | 41 | 75 |
| 2021 Abril | 69 | 59 | 128 |
| 2021 Marzo | 64 | 22 | 86 |
| 2021 Febrero | 71 | 17 | 88 |
| 2021 Enero | 32 | 22 | 54 |
| 2020 Diciembre | 36 | 12 | 48 |
| 2020 Noviembre | 21 | 20 | 41 |
| 2020 Octubre | 19 | 8 | 27 |
| 2020 Septiembre | 17 | 15 | 32 |
| 2020 Agosto | 23 | 14 | 37 |
| 2020 Julio | 25 | 13 | 38 |
| 2020 Junio | 28 | 27 | 55 |
| 2020 Mayo | 30 | 17 | 47 |
| 2020 Abril | 35 | 18 | 53 |
| 2020 Marzo | 22 | 19 | 41 |
| 2020 Febrero | 6 | 0 | 6 |
| 2020 Enero | 2 | 0 | 2 |
| 2019 Diciembre | 8 | 1 | 9 |
| 2019 Noviembre | 4 | 0 | 4 |
| 2019 Octubre | 0 | 1 | 1 |
| 2019 Septiembre | 8 | 0 | 8 |
| 2019 Agosto | 1 | 2 | 3 |
| 2019 Julio | 4 | 0 | 4 |
| 2019 Junio | 5 | 10 | 15 |
| 2019 Mayo | 4 | 36 | 40 |
| 2019 Abril | 4 | 1 | 5 |
| 2019 Marzo | 2 | 5 | 7 |
| 2019 Febrero | 2 | 0 | 2 |
| 2019 Enero | 2 | 0 | 2 |
| 2018 Diciembre | 3 | 0 | 3 |
| 2018 Noviembre | 2 | 0 | 2 |
| 2018 Octubre | 3 | 0 | 3 |
| 2018 Septiembre | 5 | 0 | 5 |
| 2018 Marzo | 3 | 0 | 3 |
| 2018 Febrero | 38 | 2 | 40 |
| 2018 Enero | 31 | 3 | 34 |
| 2017 Diciembre | 43 | 14 | 57 |
| 2017 Noviembre | 30 | 4 | 34 |
| 2017 Octubre | 38 | 4 | 42 |
| 2017 Septiembre | 24 | 2 | 26 |
| 2017 Agosto | 35 | 7 | 42 |
| 2017 Julio | 31 | 3 | 34 |
| 2017 Junio | 51 | 8 | 59 |
| 2017 Mayo | 36 | 2 | 38 |
| 2017 Abril | 28 | 5 | 33 |
| 2017 Marzo | 25 | 5 | 30 |
| 2017 Febrero | 46 | 6 | 52 |
| 2017 Enero | 31 | 7 | 38 |
| 2016 Diciembre | 72 | 5 | 77 |
| 2016 Noviembre | 59 | 11 | 70 |
| 2016 Octubre | 97 | 12 | 109 |
| 2016 Septiembre | 135 | 16 | 151 |
| 2016 Agosto | 52 | 12 | 64 |
| 2016 Julio | 38 | 6 | 44 |
| 2016 Junio | 10 | 0 | 10 |
| 2016 Mayo | 9 | 10 | 19 |
| 2016 Abril | 5 | 1 | 6 |
| 2016 Marzo | 7 | 0 | 7 |
| 2016 Febrero | 6 | 4 | 10 |
| 2016 Enero | 6 | 1 | 7 |
| 2015 Diciembre | 8 | 3 | 11 |
| 2015 Noviembre | 8 | 3 | 11 |
| 2015 Octubre | 12 | 2 | 14 |
| 2015 Septiembre | 7 | 3 | 10 |
| 2015 Agosto | 10 | 6 | 16 |
| 2015 Julio | 66 | 10 | 76 |
| 2015 Junio | 54 | 10 | 64 |
| 2015 Mayo | 70 | 6 | 76 |
| 2015 Abril | 62 | 7 | 69 |
| 2015 Marzo | 67 | 6 | 73 |
| 2015 Febrero | 51 | 8 | 59 |
| 2015 Enero | 64 | 25 | 89 |
| 2014 Diciembre | 44 | 12 | 56 |
| 2014 Noviembre | 33 | 3 | 36 |
| 2014 Octubre | 32 | 3 | 35 |
| 2014 Septiembre | 22 | 1 | 23 |
| 2014 Agosto | 25 | 4 | 29 |
| 2014 Julio | 35 | 5 | 40 |
| 2014 Junio | 40 | 3 | 43 |
| 2014 Mayo | 39 | 5 | 44 |
| 2014 Abril | 28 | 3 | 31 |
| 2014 Marzo | 24 | 10 | 34 |
| 2014 Febrero | 14 | 2 | 16 |
| 2014 Enero | 11 | 1 | 12 |
| 2013 Diciembre | 15 | 5 | 20 |
| 2013 Noviembre | 21 | 4 | 25 |
| 2013 Octubre | 14 | 2 | 16 |
| 2013 Septiembre | 12 | 1 | 13 |
| 2013 Agosto | 9 | 5 | 14 |
| 2013 Julio | 11 | 4 | 15 |
| 2013 Junio | 9 | 6 | 15 |
| 2013 Mayo | 9 | 4 | 13 |
| 2013 Abril | 17 | 6 | 23 |
| 2013 Marzo | 16 | 6 | 22 |
| 2013 Febrero | 38 | 2 | 40 |
| 2013 Enero | 47 | 6 | 53 |
| 2012 Diciembre | 30 | 5 | 35 |
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