e-Case Report
Usefulness of a Simple Immunohistochemical Staining Technique to Differentiate Anti-p200 Pemphigoid From Other Autoimmune Blistering Diseases: A Report of 2 Cases
Descripción de 2 casos de penfigoide anti-p200. Utilidad de una técnica inmunohistoquímica sencilla en el diagnóstico diferencial con otras enfermedades ampollosas autoinmunes
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Utilidad de una técnica inmunohistoquímica sencilla en el diagnóstico diferencial con otras enfermedades ampollosas autoinmunes" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "e1" "paginaFinal" => "e5" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Usefulness of a Simple Immunohistochemical Staining Technique to Differentiate Anti-p200 Pemphigoid From Other Autoimmune Blistering Diseases: A Report of 2 Cases" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figura 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1320 "Ancho" => 1650 "Tamanyo" => 277094 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">En el estudio inmunohistoquímico con colágeno <span class="elsevierStyleSmallCaps">iv</span> se observa la tinción de la parte dérmica de la ampolla, que demuestra que esta se encuentra por encima de la lámina densa, así como de la pared de los vasos dérmicos (colágeno <span class="elsevierStyleSmallCaps">iv</span> ×<span class="elsevierStyleHsp" style=""></span>200).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "I. 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Galiano Mejías, G. Carretero, C. Ferrandiz, F. Vanaclocha, E. Daudén, F.J. Gómez-García, E. Herrera-Ceballos, I. Belinchón-Romero, J.L. Sánchez-Carazo, J.L. López-Estebaranz, M. Alsina, M. Ferrán, R. Torrado, J.M. Carrascosa, R. Rivera, M. Llamas-Velasco, R. Jiménez-Puya, Mª V. Mendiola, D. Ruiz-Genao, M.A. Descalzo, P. de la Cueva Dobao" "autores" => array:22 [ 0 => array:2 [ "nombre" => "S." "apellidos" => "Galiano Mejías" ] 1 => array:2 [ "nombre" => "G." "apellidos" => "Carretero" ] 2 => array:2 [ "nombre" => "C." "apellidos" => "Ferrandiz" ] 3 => array:2 [ "nombre" => "F." "apellidos" => "Vanaclocha" ] 4 => array:2 [ "nombre" => "E." "apellidos" => "Daudén" ] 5 => array:2 [ "nombre" => "F.J." "apellidos" => "Gómez-García" ] 6 => array:2 [ "nombre" => "E." "apellidos" => "Herrera-Ceballos" ] 7 => array:2 [ "nombre" => "I." "apellidos" => "Belinchón-Romero" ] 8 => array:2 [ "nombre" => "J.L." "apellidos" => "Sánchez-Carazo" ] 9 => array:2 [ "nombre" => "J.L." 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"apellidos" => "de la Cueva Dobao" ] 21 => array:1 [ "colaborador" => "del grupo Biobadaderm" ] ] ] ] "resumen" => array:1 [ 0 => array:3 [ "titulo" => "Graphical abstract" "clase" => "graphical" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><elsevierMultimedia ident="fig0005"></elsevierMultimedia></p></span>" ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0001731016302915" "doi" => "10.1016/j.ad.2016.08.003" "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/S0001731016302915?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219016302724?idApp=UINPBA000044" "url" => "/15782190/0000010800000001/v1_201612300037/S1578219016302724/v1_201612300037/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">e-Case Report</span>" "titulo" => "Usefulness of a Simple Immunohistochemical Staining Technique to Differentiate Anti-p200 Pemphigoid From Other Autoimmune Blistering Diseases: A Report of 2 Cases" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "e1" "paginaFinal" => "e5" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "I. García-Díez, M.E. Martínez-Escala, N. Ishii, T. Hashimoto, J.M. Mascaró Galy, R.M. Pujol, J.E. Herrero-González" "autores" => array:7 [ 0 => array:4 [ "nombre" => "I." "apellidos" => "García-Díez" "email" => array:2 [ 0 => "60495@parcdesalutmar.cat" 1 => "irenegds7@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "M.E." "apellidos" => "Martínez-Escala" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "N." "apellidos" => "Ishii" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "T." "apellidos" => "Hashimoto" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "J.M." "apellidos" => "Mascaró Galy" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 5 => array:3 [ "nombre" => "R.M." "apellidos" => "Pujol" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "J.E." "apellidos" => "Herrero-González" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Departamento de Dermatología, Hospital del Mar, Parc de Salut Mar, Institut Hospital del Mar d’Investigacions Mèdiques, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Dermatología, Facultad de Medicina de la Universidad de Kurume, Fukuoka, Japan" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Departamento de Dermatología, Hospital Clínic, Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Descripción de 2 casos de penfigoide anti-p200. Utilidad de una técnica inmunohistoquímica sencilla en el diagnóstico diferencial con otras enfermedades ampollosas autoinmunes" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1000 "Ancho" => 1500 "Tamanyo" => 331362 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A, Macules and hyperpigmented plaques in the hand. B, Subepidermal blister containing abundant polymorphonuclear cells (hematoxylin-eosin, ×<span class="elsevierStyleHsp" style=""></span>200).<span class="elsevierStyleHsp" style=""></span>C, Linear deposit in the basement membrane of C3 in direct immunofluorescence. D, Weak marking of IgG class antibodies directed against the dermal side of the blister in indirect immunofluorescence of salt-split skin (sodium chloride 1<span class="elsevierStyleHsp" style=""></span>M) (antibody dilution 1/10).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Anti-p200 pemphigoid is an autoimmune subepidermal blistering disease first described by Zillikens et al.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a> in 1996 in a 54-year-old man. The patient presented with generalized bullae associated with IgG antibodies directed against a 200<span class="elsevierStyleHsp" style=""></span>kDa protein located in the lamina lucida of the basement membrane. Subsequently, 91 additional cases have been reported and the actual incidence is unknown.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We report the first 2 cases in Spain.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case Histories</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Case 1</span><p id="par0015" class="elsevierStylePara elsevierViewall">A 65-year-old man presented with a history of Horton arteritis treated with low-dose oral corticosteroids and bullous pemphigoid (BP) diagnosed 3 years earlier in another hospital. He attended our department with a new episode of pruriginous lesions. Physical examination showed tense bullae and urticarial plaques predominantly on the legs, with isolated lesions on the trunk. There was no mucosal involvement.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Biopsy of the lesioned skin showed subepidermal bullae and an inflammatory infiltrate composed of neutrophils throughout the basement membrane (BM), with papillary microabscesses of neutrophils and some foci of eosinophilic spongiosis. Direct immunofluorescence (IF) revealed linear deposits of C3 and IgG in the BM. Circulating immunoglobulin (Ig) G antibodies directed against the dermal part of the BM were detected in indirect IF of salt-split skin (sodium chloride 1<span class="elsevierStyleHsp" style=""></span>M) (<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>). Anti-BP180 and anti-collagen <span class="elsevierStyleSmallCaps">vii</span> antibodies were negative with enzyme-linked immunosorbent assay (ELISA). An immunoblot of extracts of human skin, performed according to previously described methods, detected IgG antibodies directed against a 200<span class="elsevierStyleHsp" style=""></span>kDa protein (<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>).<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">3</span></a> Treatment was initiated with topical clobetasol according to a regimen for moderate to severe BP,<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a> and the prednisone dose (10<span class="elsevierStyleHsp" style=""></span>mg/d) was maintained for arteritis, with good response. The patient had a new episode of blistering on reducing the dose of oral corticosteroids to 5<span class="elsevierStyleHsp" style=""></span>mg/d. The prednisone dose was increased to 20<span class="elsevierStyleHsp" style=""></span>mg/d and dapsone 50<span class="elsevierStyleHsp" style=""></span>mg/d was added. Clinical improvement was seen. Finally, the patient remained free of lesions with dapsone 75<span class="elsevierStyleHsp" style=""></span>mg/d and prednisone 7.5<span class="elsevierStyleHsp" style=""></span>mg/d.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Case 2</span><p id="par0025" class="elsevierStylePara elsevierViewall">The patient was a 43-year-old man with history of plaque psoriasis who, 18 months earlier, coinciding with a stressful event, had experienced an episode of tense bullae on the face, scalp, genitals, and groin, with no mucosal involvement. He was treated with prednisone at a dose of 0.5<span class="elsevierStyleHsp" style=""></span>mg/kg/d, with remission of the lesions. Subsequently, he presented with a new episode of lesions, for which he received treatment with ciclosporin (without success) in another center. He finally responded to high doses of dapsone (200<span class="elsevierStyleHsp" style=""></span>mg/d).</p><p id="par0030" class="elsevierStylePara elsevierViewall">The physical examination on his first visit showed multiple erythematous scaling plaques on the trunk and limbs, corresponding to psoriasis lesions, along with macules and hyperpigmented plaques predominantly on the arms. Skin biopsy showed subepidermal bullae with abundant polymorphonuclear cells and microabscesses of neutrophils in dermal papillae. The results of direct and indirect IF and anti-BP180 and anti-collagen <span class="elsevierStyleSmallCaps">vii</span> ELISA were identical to those described for the first patient (<a class="elsevierStyleCrossRef" href="#fig0015">Figure 3</a>). Immunohistochemical study for collagen <span class="elsevierStyleSmallCaps">iv</span> of the paraffin block was also performed, and in contrast to the first patient, intense marking of the blister floor was observed (<a class="elsevierStyleCrossRef" href="#fig0020">Figure 4</a>). Immunoblotting confirmed diagnosis of anti-p200 pemphigoid (<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Given that the lesions had practically remitted with dapsone 200<span class="elsevierStyleHsp" style=""></span>mg/d and that the patient tolerated treatment poorly due to asthenia, the dose was tapered progressively until discontinuation. During this time, the isolated appearance of blisters resolved with potent topical corticosteroids.</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Discussion</span><p id="par0040" class="elsevierStylePara elsevierViewall">Anti-p200 pemphigoid is a recently described blistering disease.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">1,2,5,6</span></a> Patients are usually middle-aged adults (<<span class="elsevierStyleHsp" style=""></span>65<span class="elsevierStyleHsp" style=""></span>years) with tense bullae and generalized urticarial pruriginous plaques, with clinical characteristics similar to BP or the inflammatory form of epidermolysis bullosa acquisita (EBA).<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2,5,6</span></a> Mucosal lesions are observed in approximately 20% of cases.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2,5,6</span></a> The bullae usually resolve without leaving scars or milia.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2,5</span></a> A high prevalence of psoriasis has been reported.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2,5–7</span></a> Some cases have been associated with drugs (penicillin) or psoralen and ultraviolet A radiation phototherapy.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">6,8</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Characteristic histopathological findings include presence of subepidermal blisters, accompanied by an inflammatory infiltrate in the superficial dermis, which is usually neutrophilic and less often eosinophilic.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2,5,6,9</span></a> Occasionally, microabscesses of neutrophils in dermal papillae and neutrophilic or eosinophilic spongiosis can be observed.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2,5,6,9</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Direct immunofluorescence (IF) reveals linear deposits of C3 and IgG in the BM. Indirect IF of salt-split skin (sodium chloride 1<span class="elsevierStyleHsp" style=""></span>M) shows circulating IgG antibodies directed against the dermal side of the blister, although deposits have occasionally been observed on both sides.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">1,2,5,6,9</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Diagnosis is established with an immunoblot of extracts of human skin, in which the serum of patients reacts to a 200<span class="elsevierStyleHsp" style=""></span>kDa protein.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">1,2,5</span></a> In 25% of cases, weaker reactivity has been observed with other antigens, such as BP180, BP230, or laminin 332. This observation may be explained by intermolecular expansion of epitopes.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2,5,6,10</span></a> Immunoblotting is a complex technique that is available in only a few laboratories. This has probably limited the diagnosis in some cases of anti-p200 pemphigoid.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Immunohistochemical study of the components of the BM in biopsies of blisters recently fixed in paraffin can usually locate collagen <span class="elsevierStyleSmallCaps">iv</span> (which labels the dense lamina) on the dermal side of the blister, thereby assisting diagnosis if immunoblotting is not available.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Currently, large gaps still remain in our knowledge of the pathogenesis of anti-p200 pemphigoid.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">2</span></a> The p200 antigen is a noncollagen protein localized at the interface between the lamina lucida and the lamina densa of the BM. Recently, laminin gamma-1 has been identified as the autoantigen in 90% of cases, with an epitope localized in residue 246 of the carboxy terminal domain.<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">5,7,11</span></a> However, all attempts to demonstrate the pathogenicity of antibodies directed against the carboxy terminal domain of laminin gamma-1 have failed.<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">12–14</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Differential diagnosis should include other subepidermal blistering diseases with C3 deposits and/or linear IgG in direct IF, mainly BP and EBA.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2,5</span></a> Indirect IF of salt-split skin (or direct IF of split skin when circulating antibodies are not detected) enables us to distinguish the entity from BP but not from EBA. In these cases, immunohistochemistry for collagen <span class="elsevierStyleSmallCaps">iv</span> is a simple technique that enables us to differentiate anti-p200 pemphigoid from EBA: collagen <span class="elsevierStyleSmallCaps">iv</span> would be present in the blister floor in the former case and in the roof of the blister in the latter case. However, this technique may not be informative in cases of intense inflammatory infiltrate.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a> These findings are not pathognomic and to establish an unequivocal diagnosis, immunoblotting or even more complex techniques such as immunoprecipitation are required.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2,5,7</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">With regard to treatment, the regimens proposed for BP are as follows: potent topical corticosteroids, prednisone 0.5<span class="elsevierStyleHsp" style=""></span>mg/kg as monotherapy or in combination with dapsone (1.5<span class="elsevierStyleHsp" style=""></span>mg/kg).<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2,5,15</span></a> The outcome after treatment is variable, but response is usually rapid and favorable to immunosuppressants.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2,5</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">In conclusion, we present the first 2 cases of anti-p200 pemphigoid described in Spain and have characterized the lesions clinically, pathologically, and immunologically. Given the difficult techniques required for diagnosis, it is likely that anti-p200 pemphigoid is underdiagnosed, with cases erroneously classified as BP or EBA. Differential diagnosis with respect to EBA is particularly important as both entities differ substantially in terms of management and prognosis. We propose immunohistochemistry with collagen <span class="elsevierStyleSmallCaps">iv</span> of lesioned skin, combining it with the usual IF techniques, as a simple and accessible tool for differential diagnosis with EAA.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Ethical Responsibilities</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Protection of human and animal subjects</span><p id="par0085" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this investigation.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Confidentiality of data</span><p id="par0090" class="elsevierStylePara elsevierViewall">The authors declare that they have followed their hospital's protocol on the publication of data concerning patients.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Right to privacy and informed consent</span><p id="par0095" class="elsevierStylePara elsevierViewall">The authors obtained the informed consent of patients and/or subjects mentioned in this article. The informed consent form is located in the archives of the corresponding author.</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Funding</span><p id="par0100" class="elsevierStylePara elsevierViewall">The study was partially funded with Research Project PI 09/1410 (J. Herrero), with cofunding from FEDER.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conflicts of Interest</span><p id="par0105" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres783876" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec782761" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres783875" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec782762" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Case Histories" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Case 1" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Case 2" ] ] ] 6 => array:2 [ "identificador" => "sec0025" "titulo" => "Discussion" ] 7 => array:3 [ "identificador" => "sec0030" "titulo" => "Ethical Responsibilities" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0040" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0045" "titulo" => "Right to privacy and informed consent" ] ] ] 8 => array:2 [ "identificador" => "sec0050" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0055" "titulo" => "Conflicts of Interest" ] 10 => array:2 [ "identificador" => "xack262398" "titulo" => "Acknowledgments" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec782761" "palabras" => array:5 [ 0 => "Laminin gamma 1" 1 => "Anti-p200 pemphigoid" 2 => "Bullous skin diseases" 3 => "Immunoblotting" 4 => "Collagen type IV" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec782762" "palabras" => array:5 [ 0 => "Laminina gamma-1" 1 => "Penfigoide anti-p200" 2 => "Enfermedades ampollosas" 3 => "Inmunoblot" 4 => "Colágeno tipo <span class="elsevierStyleSmallCaps">IV</span>" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Anti-p200 pemphigoid is a rare autoimmune subepidermal blistering disease characterized by the presence of circulating immunoglobulin G antibodies directed against laminin gamma-1, a 200-kDa protein located in the lamina lucida of the basement membrane. We review the clinical, histopathological and immunological characteristics of the first 2 cases described in Spain. Anti-p200 pemphigoid shares histopathological and immunopathological findings with epidermolysis bullosa acquisita, the main entity in the differential diagnosis. However, its management follows the same guidelines as those used for bullous pemphigoid. The diagnosis is confirmed by immunoblotting, which is a complex technique available in few centers. We propose the immunohistochemical detection of collagen type <span class="elsevierStyleSmallCaps">IV</span> on the floor of the blister, combined with standard immunofluorescence techniques, as a simple, accessible alternative to differentiate anti-p200 pemphigoid from epidermolysis bullosa acquisita.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El penfigoide anti-p200 es una enfermedad ampollosa subepidérmica autoinmune infrecuente, asociada a la presencia de anticuerpos circulantes de tipo IgG dirigidos frente a la laminina gamma-1, una proteína de 200<span class="elsevierStyleHsp" style=""></span>kDa localizada en la lámina lúcida de la membrana basal. Revisamos las características clínicas, histopatológicas e inmunológicas de los 2 primeros casos descritos en España. El penfigoide anti-p200 comparte hallazgos histopatológicos e inmunopatológicos con la epidermólisis ampollosa adquirida, su principal diagnóstico diferencial. Sin embargo, su manejo sigue las mismas pautas descritas para el penfigoide ampolloso. El diagnóstico se confirma mediante <span class="elsevierStyleItalic">inmunoblot</span>, una técnica compleja y accesible en pocos centros. Proponemos la detección mediante inmunohistoquímica del colágeno <span class="elsevierStyleSmallCaps">iv</span> en el suelo de la ampolla, combinándola con las técnicas habituales de inmunofluorescencia, como alternativa sencilla y disponible, para diferenciarlo de la epidermólisis ampollosa adquirida.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: García-Díez I, Martínez-Escala ME, Ishii N, Hashimoto T, Galy JMM, Pujol RM, et al. Descripción de 2 casos de penfigoide anti-p200. Utilidad de una técnica inmunohistoquímica sencilla en el diagnóstico diferencial con otras enfermedades ampollosas autoinmunes. Actas Dermosifiliogr. 2017;108:e1–e5.</p>" ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1068 "Ancho" => 1602 "Tamanyo" => 299193 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A and B, Tense bullae on an urticarial base located on the knee and ankle. C, Neutrophilic infiltrate with some eosinophils throughout the basement membrane, with formation of papillary microabscesses (hematoxylin-eosin ×<span class="elsevierStyleHsp" style=""></span>200). D, Presence of IgG class antibodies directed against the dermal side of the blister in indirect immunofluorescence of salt-split skin (sodium chloride 1<span class="elsevierStyleHsp" style=""></span>M) (1/40 antibody dilution).</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1924 "Ancho" => 1549 "Tamanyo" => 182672 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Immunoblot technique performed with dermal extracts of human skin, obtained by splitting skin with ethylenediamine tetraacetic acid and submitting to electrophoresis on SDS-polyacrylamide gel, as per the Laemmli method (left) as well as immunoblotting with recombinant laminin 332 (right). As shown in the left panel (dermal extracts of human skin), sera of patients 1 and 2 (corresponding to columns 3 and 4, respectively) show a band at 200<span class="elsevierStyleHsp" style=""></span>kDa, corresponding to the same band present in the serum of another patient with anti-p200 pemphigoid (column 2). This band is not present in the serum of a patient with epidermolysis bullosa acquisita (column 1), but a band is present at 290<span class="elsevierStyleHsp" style=""></span>kDa, corresponding to collagen <span class="elsevierStyleSmallCaps">vii</span>. In the right panel (recombinant laminin 332), the recombinant protein is not detected in the sera of patients 1 and 2 (columns 3 and 4, respectively) and the serum from healthy control (column 2), whereas the serum of a patient with anti-laminin 332 pemphigoid (column 1) has several bands at 165, 145, 140, and 105 140<span class="elsevierStyleHsp" style=""></span>kDa, corresponding to the α3, β3, and γ2 chains of laminin 332, respectively.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1000 "Ancho" => 1500 "Tamanyo" => 331362 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A, Macules and hyperpigmented plaques in the hand. B, Subepidermal blister containing abundant polymorphonuclear cells (hematoxylin-eosin, ×<span class="elsevierStyleHsp" style=""></span>200).<span class="elsevierStyleHsp" style=""></span>C, Linear deposit in the basement membrane of C3 in direct immunofluorescence. D, Weak marking of IgG class antibodies directed against the dermal side of the blister in indirect immunofluorescence of salt-split skin (sodium chloride 1<span class="elsevierStyleHsp" style=""></span>M) (antibody dilution 1/10).</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 792 "Ancho" => 990 "Tamanyo" => 140247 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Immunohistochemical study with collagen <span class="elsevierStyleSmallCaps">iv</span>, showing staining of the dermal part of the blister, thus demonstrating that the collagen is above the lamina densa, as well as the wall of dermal vessels (collagen <span class="elsevierStyleSmallCaps">iv</span> ×<span class="elsevierStyleHsp" style=""></span>200).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0080" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A novel subepidermal blistering disease with autoantibodies to a 200-kDa antigen of the basement membrane zone" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 9 | 13 | 22 |
| 2024 Octubre | 90 | 42 | 132 |
| 2024 Septiembre | 109 | 23 | 132 |
| 2024 Agosto | 126 | 45 | 171 |
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| 2023 Noviembre | 79 | 32 | 111 |
| 2023 Octubre | 73 | 25 | 98 |
| 2023 Septiembre | 91 | 36 | 127 |
| 2023 Agosto | 70 | 13 | 83 |
| 2023 Julio | 89 | 34 | 123 |
| 2023 Junio | 100 | 32 | 132 |
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| 2023 Abril | 55 | 22 | 77 |
| 2023 Marzo | 78 | 28 | 106 |
| 2023 Febrero | 80 | 34 | 114 |
| 2023 Enero | 57 | 30 | 87 |
| 2022 Diciembre | 76 | 40 | 116 |
| 2022 Noviembre | 31 | 37 | 68 |
| 2022 Octubre | 42 | 21 | 63 |
| 2022 Septiembre | 27 | 38 | 65 |
| 2022 Agosto | 32 | 39 | 71 |
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| 2022 Junio | 45 | 27 | 72 |
| 2022 Mayo | 84 | 45 | 129 |
| 2022 Abril | 125 | 42 | 167 |
| 2022 Marzo | 133 | 62 | 195 |
| 2022 Febrero | 129 | 58 | 187 |
| 2022 Enero | 126 | 43 | 169 |
| 2021 Diciembre | 86 | 60 | 146 |
| 2021 Noviembre | 87 | 59 | 146 |
| 2021 Octubre | 63 | 62 | 125 |
| 2021 Septiembre | 51 | 42 | 93 |
| 2021 Agosto | 52 | 54 | 106 |
| 2021 Julio | 35 | 40 | 75 |
| 2021 Junio | 46 | 33 | 79 |
| 2021 Mayo | 60 | 63 | 123 |
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| 2021 Marzo | 68 | 42 | 110 |
| 2021 Febrero | 53 | 33 | 86 |
| 2021 Enero | 33 | 33 | 66 |
| 2020 Diciembre | 35 | 30 | 65 |
| 2020 Noviembre | 25 | 27 | 52 |
| 2020 Octubre | 29 | 13 | 42 |
| 2020 Septiembre | 40 | 26 | 66 |
| 2020 Agosto | 38 | 24 | 62 |
| 2020 Julio | 35 | 17 | 52 |
| 2020 Junio | 35 | 35 | 70 |
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| 2020 Enero | 4 | 0 | 4 |
| 2019 Diciembre | 8 | 0 | 8 |
| 2019 Noviembre | 4 | 0 | 4 |
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| 2019 Agosto | 7 | 0 | 7 |
| 2019 Julio | 4 | 0 | 4 |
| 2019 Junio | 6 | 0 | 6 |
| 2019 Mayo | 2 | 1 | 3 |
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| 2019 Marzo | 2 | 0 | 2 |
| 2019 Febrero | 1 | 0 | 1 |
| 2019 Enero | 2 | 0 | 2 |
| 2018 Diciembre | 2 | 0 | 2 |
| 2018 Noviembre | 1 | 0 | 1 |
| 2018 Octubre | 3 | 0 | 3 |
| 2018 Septiembre | 3 | 0 | 3 |
| 2018 Febrero | 26 | 2 | 28 |
| 2018 Enero | 37 | 14 | 51 |
| 2017 Diciembre | 41 | 16 | 57 |
| 2017 Noviembre | 50 | 10 | 60 |
| 2017 Octubre | 37 | 14 | 51 |
| 2017 Septiembre | 34 | 7 | 41 |
| 2017 Agosto | 33 | 9 | 42 |
| 2017 Julio | 18 | 11 | 29 |
| 2017 Junio | 56 | 11 | 67 |
| 2017 Mayo | 40 | 15 | 55 |
| 2017 Abril | 35 | 24 | 59 |
| 2017 Marzo | 44 | 32 | 76 |
| 2017 Febrero | 55 | 43 | 98 |
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| 2016 Diciembre | 12 | 16 | 28 |
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