Opinion Article
Ichthyosis keeps surprising us
La ictiosis nos sigue sorprendiendo
H. Traupe
Department of Dermatology, University of Münster, Münster, Germany
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"apellidos" => "Traupe" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S1578219013000899" "doi" => "10.1016/j.adengl.2012.10.010" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219013000899?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731012005194?idApp=UINPBA000044" "url" => "/00017310/0000010400000004/v1_201304241400/S0001731012005194/v1_201304241400/en/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S1578219013000607" "issn" => "15782190" "doi" => "10.1016/j.adengl.2011.11.021" "estado" => "S300" "fechaPublicacion" => "2013-05-01" "aid" => "624" "copyright" => "Elsevier España, S.L. and AEDV" "documento" => "article" "crossmark" => 0 "subdocumento" => "ssu" "cita" => "Actas Dermosifiliogr. 2013;104:270-84" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 12140 "formatos" => array:3 [ "EPUB" => 45 "HTML" => 10016 "PDF" => 2079 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review</span>" "titulo" => "Autosomal Recessive Congenital Ichthyosis" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "270" "paginaFinal" => "284" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Ictiosis congénitas autosómicas recesivas" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1050 "Ancho" => 2333 "Tamanyo" => 344283 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Clinical features of lamellar ichthyosis. A, Brownish lamellar desquamation. B, Marked plantar hyperkeratosis. C, Scarring alopecia of the scalp.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "L. Rodríguez-Pazos, M. Ginarte, A. Vega, J. Toribio" "autores" => array:4 [ 0 => array:2 [ "nombre" => "L." "apellidos" => "Rodríguez-Pazos" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Ginarte" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Vega" ] 3 => array:2 [ "nombre" => "J." "apellidos" => "Toribio" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0001731012001998" "doi" => "10.1016/j.ad.2011.11.015" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731012001998?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219013000607?idApp=UINPBA000044" "url" => "/15782190/0000010400000004/v1_201304291101/S1578219013000607/v1_201304291101/en/main.assets" ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Opinion Article</span>" "titulo" => "Ichthyosis keeps surprising us" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "267" "paginaFinal" => "269" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "H. Traupe" "autores" => array:1 [ 0 => array:3 [ "nombre" => "H." "apellidos" => "Traupe" "email" => array:1 [ 0 => "traupeh@ukmuenster.de" ] ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Department of Dermatology, University of Münster, Münster, Germany" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La ictiosis nos sigue sorprendiendo" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">In clinical practice, the pediatric dermatologist from time to time encounters patients who have ichthyosis. Patients with this rare disease need a precise diagnosis, good advice on how to manage their skin condition, and adequate genetic counseling. The old days, when ichthyosis was categorized into only 6 major types are long gone.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> A recent consensus conference revised the nomenclature and proposed a new classification that distinguishes 36 different types of ichthyosis and 10 related clinical entities (for example, CHILD-syndrome).<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Major consensus was achieved on the proposal to categorize ichthyosis into two types: nonsyndromic, in which the phenotypic expression of the underlying genetic defect is only seen in the skin; and syndromic, in which the phenotypic expression of the underlying genetic defect is seen in the skin and other organs. This new classification was a major topic at the recent ichthyosis conference <span class="elsevierStyleItalic">Jornada de ictiosis</span> organized by Dr. Ángela Hernández Martín in Madrid.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Ichthyosis vulgaris and atopic dermatitis: An intriguing relationship</span><p id="par0010" class="elsevierStylePara elsevierViewall">In the last six years, we have learned a lot about ichthyosis and both patients and also dermatology as a specialty, have benefited greatly. As recently as 2006, ichthyosis vulgaris was shown to be the result of filaggrin mutations,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> a discovery that quickly led to the insight that the very same loss-of-function mutations that cause ichthyosis vulgaris also confer a strong predisposition to atopic dermatitis.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> These discoveries sparked renewed interest in the function of filaggrin and its role in the epidermal barrier. Animal studies using a genetic mouse model of ichthyosis vulgaris (flaky tail [ft/ft]) mice demonstrate abnormalities in barrier function in association with an absence of filaggrin.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">However, some riddles remain. Given the evidence of impaired cohesiveness in the stratum corneum in ichthyosis vulgaris, one would expect that barrier function parameters, such as transepidermal water loss (TEWL), skin hydration, and skin surface pH, would be profoundly affected in these patients. Surprisingly, studies to date reveal a rather moderate effect: for example, an increase in TEWL of less than 30% and only in patients with 2 filaggrin mutations<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,7</span></a>; and a reduction in skin hydration of around 30%.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> The same applies to skin surface pH, which has been shown to be only modestly elevated in two studies<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,8</span></a>; in our own series of ichthyosis vulgaris patients having two filaggrin-mutations only a trend toward a slightly increased surface pH was observed. Moreover, no significant effect on epidermal barrier function has as yet been demonstrated in patients with mild ichthyosis vulgaris who have only one filaggrin-mutation.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Interestingly, only around 50% of patients with ichthyosis vulgaris develop atopic dermatitis, and a further 20% develop other atopic diseases, such as allergic rhinitis or bronchial asthma. Thus, a significant proportion of these patients do not develop any atopic disease.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Thus filaggrin mutations predispose patients to atopic diseases but are not sufficient by themselves to cause such conditions. In the future, biochemical studies of epidermal barrier function in patients with ichthyosis vulgaris may provide an answer as to how it is possible to prevent the onset of diseases such as atopic dermatitis despite high risk (for example, in patients with 2 filaggrin-mutations). The results of preliminary studies into this question by our group appear to imply that epidermal proteases imbalances may be a factor.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Hypohidrosis – an underestimated clinical problem</span><p id="par0025" class="elsevierStylePara elsevierViewall">The well-known symptoms of autosomal recessive congenital ichthyosis (ARCI) are severe scaling, severe cosmetic disfigurement, skin inflammation, and in some cases significant pruritus. What is often overlooked is the fact that most of these patients can hardly perspire. Many report that the only area of skin on their bodies that can sweat is their nose! In summer, even in cooler European countries such as Germany, this hypohidrosis results in severe thermodysregulation and heat intolerance. In my personal experience, some ARCI patients who exhibit only mild scaling have pronounced hypohidrosis. Treatments such as topical urea ointments often have very little effect on this symptom. In contrast, oral retinoids, such as acitretin, can be a very effective remedy resulting in normalization of sweat gland function, as demonstrated by gravimetric measurement of sweat rates before and after treatment.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> This finding suggests that hypohidrosis in ARCI and other types of ichthyosis may be due to altered sweat gland function rather than to obstruction of sweat gland ducts.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Novel clinical entities</span><p id="par0030" class="elsevierStylePara elsevierViewall">Another surprising facet of this disease is that novel clinical entities continue to emerge. Thus, inflammatory type B peeling skin syndrome has been considered to be a clinical variant of the Netherton syndrome featuring erythroderma and extensive skin peeling.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> However, true peeling skin syndrome does exist and was recently shown to be due to loss-of-function mutations in the gene for corneodesmosin.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> It shares a number of clinical features with Netherton syndrome – including erythroderma, extensive skin peeling, pruritus, and atopy in the form of food allergies and highly elevated total IgE levels – but lacks the hair abnormality (trichorrhexis invaginata) so typical of that syndrome.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Exfoliative ichthyosis<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> is another disease characterized by erythroderma at birth and slight hyperkeratosis accompanied by exfoliation in later life. The clinical hallmark of this condition is the water sensitive palmoplantar keratoderma that distinguishes it from type B peeling skin syndrome. This type of keratoderma is markedly exacerbated by exposure to moisture, with patients’ hands and feet resembling the fingers of washing women who have manually washed clothes for several hours. Surprisingly, loss-of-function mutations in the gene encoding cystatin A have been identified in this disease. Like LEKTI, cystatin A is a component of the cornified envelope and a protease inhibitor that can inhibit dust mite allergens, such as the dust mite-derived cysteine proteases Der p1 and Der f1.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Although cystatin A is involved in processes such as sensitization against house dust mite, it may have other biological roles in the lower epidermis. Interestingly, in water sensitive plantar keratoderma, electron microscopy reveals prominent intercellular edema of the suprabasal and basal cell layers and aggregation of tonofilaments, implying that skin peeling originates at the basal/suprabasal level.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Bathing and bath additives rediscovered</span><p id="par0040" class="elsevierStylePara elsevierViewall">Several years ago, patients with ichthyosis were strongly discouraged from bathing by many dermatologists, who felt that it would negatively affect skin surface pH for all skin diseases. Today we know that ichthyosis patients should take a cleansing bath daily and rub their skin with special gloves to mechanically remove some of their scales. In many, although not all patients, this mechanical scale removal is greatly facilitated by adding two handfuls of sodium bicarbonate (baking powder) to the bath water. This therapy, developed by our late colleague and friend Wolfgang Küster,<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> has also been used successfully in the United States.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> The mechanisms underlying the usefulness of sodium bicarbonate as a bath additive in this setting have not yet been well studied; however the addition of sodium bicarbonate to bath water raises the pH (from 5.5 to 7.9 in the example cited).<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> We now know that normal desquamation requires the enzymatic dissolution of corneodesmosomes by KLK5 and KLK7 and that these serine proteases have alkaline pH optima.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Topical retinoids rediscovered</span><p id="par0045" class="elsevierStylePara elsevierViewall">In the past, pharmaceutical companies have neglected ichthyosis and focused on common dermatologic conditions, such as acne, rosacea, and psoriasis. However, there is now a renewed interest in ichthyosis and scaly skin, and 2 topical retinoids are currently in clinical trials. One of these is tazarotene, which has produced quite promising results in a Phase II trial. The other is still in phase II. Moreover, a large multicenter clinical trial has been undertaken with the drug liarozol in the management of ARCI. Although the clinicians involved in this study observed a significant beneficial effect on scaling, the primary endpoint chosen (investigator global assessment) was not achieved, a good example of the difficulties involved in choosing appropriate endpoints and in study design (for example, the need for large control group when studying rare diseases). However, there is hope that the overall encouraging experience with liarozol will stimulate the pharmaceutical companies to continue to explore this option. The future, of course, lies with targeted therapies. Using a skin humanized mouse model, a Spanish–German collaboration has assembled the first experimental evidence showing that topical enzyme replacement therapy with an enzyme solution containing transglutaminase-1-liposomes has convincing effects on scaling and on restoring epidermal architecture in transglutaminase-deficient lamellar ichthyosis.</p><p id="par0050" class="elsevierStylePara elsevierViewall">To sum up, ichthyosis research has helped us to gain a much better understanding of the mechanisms involved in epidermal differentiation, and ichthyoses can be regarded as diseases of the epidermal barrier. We are beginning to understand how deficiencies in epidermal barrier constituents, such as filaggrin and corneodesmosin, and the lack of a serine protease inhibitor (LEKTI) can give rise to a non-cohesive stratum corneum and contribute to allergic sensitization and atopic diseases. At the same time, we are witnessing the rediscovery of the usefulness of bathing and bath additives, such as sodium bicarbonate, as an efficient low technology strategy for combating excessive scaling, and the introduction of topical retinoids for the treatment of scaly skin. Ichthyosis really keeps surprising us.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Ichthyosis vulgaris and atopic dermatitis: An intriguing relationship" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Hypohidrosis – an underestimated clinical problem" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Novel clinical entities" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "Bathing and bath additives rediscovered" ] 4 => array:2 [ "identificador" => "sec0025" "titulo" => "Topical retinoids rediscovered" ] 5 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Traupe H. Ichthyosis keeps surprising us. Actas Dermosifiliogr. 2013;267–9.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:18 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Less common scaling dermatoses" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "P. Frost" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:5 [ "titulo" => "The ichthyoses" "paginaInicial" => "107" "paginaFinal" => "126" "edicion" => "1st ed." "serieFecha" => "1978" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "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" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F.J. Smith" 1 => "A.D. Irvine" 2 => "A. Terron-Kwiatkowski" 3 => "A. Sandilands" 4 => "L.E. Campbell" 5 => "Y. Zhao" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ng1743" "Revista" => array:6 [ "tituloSerie" => "Nat Genet" "fecha" => "2006" "volumen" => "38" "paginaInicial" => "337" "paginaFinal" => "342" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16444271" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Sandilands" 1 => "A. Terron-Kwiatkowski" 2 => "P.R. Hull" 3 => "G.M. O’Regan" 4 => "T.H. Clayton" 5 => "R.M. Watson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ng2020" "Revista" => array:6 [ "tituloSerie" => "Nat Genet" "fecha" => "2007" "volumen" => "39" "paginaInicial" => "650" "paginaFinal" => "654" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17417636" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A homozygous frameshift mutation in the mouse Flg gene facilitates enhanced percutaneous allergen priming" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.G. Fallon" 1 => "T. Sasaki" 2 => "A. Sandilands" 3 => "L.E. Campbell" 4 => "S.P. Saunders" 5 => "N.E. Mangan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ng.358" "Revista" => array:6 [ "tituloSerie" => "Nat Genet" "fecha" => "2009" "volumen" => "41" "paginaInicial" => "602" "paginaFinal" => "608" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19349982" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Filaggrin genotype in ichthyosis vulgaris predicts abnormalities in epidermal structure and function" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Gruber" 1 => "P.M. Elias" 2 => "D. Crumrine" 3 => "T.K. Lin" 4 => "J.M. Brandner" 5 => "J.P. Hachem" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ajpath.2011.01.053" "Revista" => array:6 [ "tituloSerie" => "Am J Pathol" "fecha" => "2011" "volumen" => "178" "paginaInicial" => "2252" "paginaFinal" => "2263" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21514438" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Perusquia-Ortiz AM, Oji V, Sauerland MC, Tarinski T, Zaraeva I, Aufenvenne K, Seller N, Metze D, Hausser I, Traupe H. Complete filaggrin deficiency in ichthyosis vulgaris is associated with only moderate changes in epidermal permeability barrier function profile. JEADV. In press. http://dx.doi.org//10.1111/jdv.2012.12079." ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Filaggrin genotype determines functional and molecular alterations in skin of patients with atopic dermatitis and ichthyosis vulgaris" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.C. Winge" 1 => "T. Hoppe" 2 => "B. Berne" 3 => "A. Vahlquist" 4 => "M. Nordenskjöld" 5 => "M. Bradley" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0028254" "Revista" => array:5 [ "tituloSerie" => "PLoS ONE" "fecha" => "2011" "volumen" => "6" "paginaInicial" => "e28254" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22164253" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ichthyosis vulgaris: novel FLG mutations in the German population and high presence of CD1a+ cells in the epidermis of the atopic subgroup" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V. Oji" 1 => "N. Seller" 2 => "A. Sandilands" 3 => "R. Gruber" 4 => "J. Gerss" 5 => "U. Hüffmeier" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2133.2008.08999.x" "Revista" => array:6 [ "tituloSerie" => "Br J Dermatol" "fecha" => "2009" "volumen" => "160" "paginaInicial" => "771" "paginaFinal" => "781" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19183181" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effective treatment of severe thermodysregulation by oral retinoids in a patient with recessive congenital lamellar ichthyosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H.A. Haenssle" 1 => "A. Finkenrath" 2 => "I. Hausser" 3 => "V. Oji" 4 => "H. Traupe" 5 => "H.C. Hennies" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2230.2008.02709.x" "Revista" => array:6 [ "tituloSerie" => "Clin Exp Dermatol" "fecha" => "2008" "volumen" => "33" "paginaInicial" => "578" "paginaFinal" => "581" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18355358" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Netherton syndrome with extensive skin peeling and failure to thrive due to a homozygous frameshift mutation in SPINK5" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A.S. Geyer" 1 => "P. Ratajczak" 2 => "M. Pol-Rodriguez" 3 => "W.S. Millar" 4 => "M. Garzon" 5 => "G. Richard" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1159/000084755" "Revista" => array:6 [ "tituloSerie" => "Dermatology" "fecha" => "2005" "volumen" => "210" "paginaInicial" => "308" "paginaFinal" => "314" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15942217" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Loss of corneodesmosin leads to severe skin barrier defect, pruritus, and atopy: unraveling the peeling skin disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V. Oji" 1 => "K.M. Eckl" 2 => "K. Aufenvenne" 3 => "M. Nätebus" 4 => "T. Tarinski" 5 => "K. Ackermann" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ajhg.2010.07.005" "Revista" => array:6 [ "tituloSerie" => "Am J Hum Genet" "fecha" => "2010" "volumen" => "87" "paginaInicial" => "274" "paginaFinal" => "281" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20691404" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "An autosomal recessive exfoliative ichthyosis with linkage to chromosome 12q13" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S.J. Hatsell" 1 => "H. Stevens" 2 => "A.P. Jackson" 3 => "D.P. Kelsell" 4 => "A. Zvulunov" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Br J Dermatol" "fecha" => "2003" "volumen" => "149" "paginaInicial" => "174" "paginaFinal" => "180" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12890214" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cystatin A inhibits IL-8 production by keratinocytes stimulated with Der p 1 and Der f 1: biochemical skin barrier against mite cysteine proteases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "T. Kato" 1 => "T. Takai" 2 => "K. Mitsuishi" 3 => "K. Okumura" 4 => "H. Ogawa" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaci.2005.03.044" "Revista" => array:7 [ "tituloSerie" => "J Allergy Clin Immunol" "fecha" => "2005" "volumen" => "116" "paginaInicial" => "169" "paginaFinal" => "176" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15990791" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0010782408005428" "estado" => "S300" "issn" => "00107824" ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mutations in CSTA, encoding Cystatin A, underlie exfoliative ichthyosis and reveal a role for this protease inhibitor in cell–cell adhesion" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.C. Blaydon" 1 => "D. Nitoiu" 2 => "K.M. Eckl" 3 => "R.M. Cabral" 4 => "P. Bland" 5 => "I. Hausser" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ajhg.2011.09.001" "Revista" => array:6 [ "tituloSerie" => "Am J Hum Genet" "fecha" => "2011" "volumen" => "89" "paginaInicial" => "564" "paginaFinal" => "571" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21944047" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment of ichthyosis—there is always something you can do! In memoriam: Wolfgang Küster" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "H. Traupe" 1 => "W.H.C. Burgdorf" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "2007" "volumen" => "57" "paginaInicial" => "542" "paginaFinal" => "547" ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Scaly skin and bath pH: rediscovering baking soda" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "L.M. Milstone" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaad.2009.04.011" "Revista" => array:6 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "2010" "volumen" => "62" "paginaInicial" => "885" "paginaFinal" => "886" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20398816" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A proteolytic cascade of kallikreins in the stratum corneum" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Brattsand" 1 => "K. Stefansson" 2 => "C. Lundh" 3 => "Y. Haasum" 4 => "T. Egelrud" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.0022-202X.2004.23547.x" "Revista" => array:6 [ "tituloSerie" => "J Invest Dermatol" "fecha" => "2005" "volumen" => "124" "paginaInicial" => "198" "paginaFinal" => "203" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15654974" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/15782190/0000010400000004/v1_201304291101/S1578219013000899/v1_201304291101/en/main.assets" "Apartado" => array:4 [ "identificador" => "6152" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Opinion Article" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15782190/0000010400000004/v1_201304291101/S1578219013000899/v1_201304291101/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219013000899?idApp=UINPBA000044" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 20 | 14 | 34 |
| 2024 October | 78 | 48 | 126 |
| 2024 September | 83 | 20 | 103 |
| 2024 August | 104 | 59 | 163 |
| 2024 July | 86 | 33 | 119 |
| 2024 June | 86 | 33 | 119 |
| 2024 May | 67 | 38 | 105 |
| 2024 April | 64 | 25 | 89 |
| 2024 March | 70 | 42 | 112 |
| 2024 February | 76 | 51 | 127 |
| 2024 January | 48 | 37 | 85 |
| 2023 December | 73 | 19 | 92 |
| 2023 November | 67 | 35 | 102 |
| 2023 October | 68 | 78 | 146 |
| 2023 September | 64 | 67 | 131 |
| 2023 August | 41 | 36 | 77 |
| 2023 July | 38 | 59 | 97 |
| 2023 June | 49 | 47 | 96 |
| 2023 May | 69 | 78 | 147 |
| 2023 April | 34 | 42 | 76 |
| 2023 March | 42 | 70 | 112 |
| 2023 February | 60 | 48 | 108 |
| 2023 January | 40 | 53 | 93 |
| 2022 December | 38 | 46 | 84 |
| 2022 November | 32 | 53 | 85 |
| 2022 October | 25 | 35 | 60 |
| 2022 September | 24 | 110 | 134 |
| 2022 August | 26 | 49 | 75 |
| 2022 July | 16 | 48 | 64 |
| 2022 June | 23 | 46 | 69 |
| 2022 May | 30 | 55 | 85 |
| 2022 April | 34 | 51 | 85 |
| 2022 March | 45 | 55 | 100 |
| 2022 February | 35 | 32 | 67 |
| 2022 January | 30 | 38 | 68 |
| 2021 December | 27 | 48 | 75 |
| 2021 November | 28 | 52 | 80 |
| 2021 October | 32 | 50 | 82 |
| 2021 September | 23 | 41 | 64 |
| 2021 August | 22 | 35 | 57 |
| 2021 July | 16 | 40 | 56 |
| 2021 June | 16 | 24 | 40 |
| 2021 May | 24 | 51 | 75 |
| 2021 April | 71 | 69 | 140 |
| 2021 March | 64 | 48 | 112 |
| 2021 February | 47 | 42 | 89 |
| 2021 January | 39 | 27 | 66 |
| 2020 December | 31 | 35 | 66 |
| 2020 November | 28 | 19 | 47 |
| 2020 October | 28 | 29 | 57 |
| 2020 September | 34 | 16 | 50 |
| 2020 August | 18 | 26 | 44 |
| 2020 July | 24 | 30 | 54 |
| 2020 June | 26 | 29 | 55 |
| 2020 May | 22 | 25 | 47 |
| 2020 April | 25 | 39 | 64 |
| 2020 March | 23 | 34 | 57 |
| 2020 February | 2 | 16 | 18 |
| 2020 January | 4 | 12 | 16 |
| 2019 December | 8 | 12 | 20 |
| 2019 November | 4 | 12 | 16 |
| 2019 October | 0 | 7 | 7 |
| 2019 September | 7 | 6 | 13 |
| 2019 August | 4 | 5 | 9 |
| 2019 July | 5 | 19 | 24 |
| 2019 June | 6 | 19 | 25 |
| 2019 May | 4 | 59 | 63 |
| 2019 April | 3 | 41 | 44 |
| 2019 March | 4 | 10 | 14 |
| 2019 February | 0 | 8 | 8 |
| 2019 January | 4 | 7 | 11 |
| 2018 December | 1 | 12 | 13 |
| 2018 November | 3 | 3 | 6 |
| 2018 October | 3 | 0 | 3 |
| 2018 September | 1 | 4 | 5 |
| 2018 August | 0 | 8 | 8 |
| 2018 July | 0 | 7 | 7 |
| 2018 June | 0 | 11 | 11 |
| 2018 May | 0 | 9 | 9 |
| 2018 April | 0 | 10 | 10 |
| 2018 March | 0 | 3 | 3 |
| 2018 February | 16 | 12 | 28 |
| 2018 January | 34 | 8 | 42 |
| 2017 December | 34 | 9 | 43 |
| 2017 November | 30 | 7 | 37 |
| 2017 October | 24 | 13 | 37 |
| 2017 September | 24 | 17 | 41 |
| 2017 August | 40 | 17 | 57 |
| 2017 July | 22 | 15 | 37 |
| 2017 June | 30 | 20 | 50 |
| 2017 May | 24 | 13 | 37 |
| 2017 April | 23 | 12 | 35 |
| 2017 March | 17 | 16 | 33 |
| 2017 February | 24 | 10 | 34 |
| 2017 January | 14 | 26 | 40 |
| 2016 December | 27 | 5 | 32 |
| 2016 November | 23 | 14 | 37 |
| 2016 October | 47 | 11 | 58 |
| 2016 September | 39 | 19 | 58 |
| 2016 August | 35 | 13 | 48 |
| 2016 July | 23 | 7 | 30 |
| 2016 June | 10 | 9 | 19 |
| 2016 May | 3 | 9 | 12 |
| 2016 April | 7 | 10 | 17 |
| 2016 March | 4 | 7 | 11 |
| 2016 February | 6 | 1 | 7 |
| 2016 January | 9 | 1 | 10 |
| 2015 December | 7 | 1 | 8 |
| 2015 November | 5 | 4 | 9 |
| 2015 October | 8 | 4 | 12 |
| 2015 September | 10 | 1 | 11 |
| 2015 August | 18 | 0 | 18 |
| 2015 July | 30 | 116 | 146 |
| 2015 June | 34 | 15 | 49 |
| 2015 May | 38 | 17 | 55 |
| 2015 April | 11 | 3 | 14 |
| 2015 March | 14 | 8 | 22 |
| 2015 February | 11 | 6 | 17 |
| 2015 January | 5 | 2 | 7 |
| 2014 December | 12 | 4 | 16 |
| 2014 November | 4 | 6 | 10 |
| 2014 October | 17 | 7 | 24 |
| 2014 September | 6 | 5 | 11 |
| 2014 August | 9 | 5 | 14 |
| 2014 July | 2 | 7 | 9 |
| 2014 June | 14 | 6 | 20 |
| 2014 May | 18 | 8 | 26 |
| 2014 April | 16 | 5 | 21 |
| 2014 March | 17 | 7 | 24 |
| 2014 February | 22 | 4 | 26 |
| 2014 January | 11 | 8 | 19 |
| 2013 December | 20 | 9 | 29 |
| 2013 November | 17 | 5 | 22 |
| 2013 October | 4 | 3 | 7 |
| 2013 September | 1 | 1 | 2 |
| 2013 August | 3 | 2 | 5 |
| 2013 July | 2 | 7 | 9 |
| 2013 June | 2 | 3 | 5 |
| 2013 May | 4 | 1 | 5 |
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