Letter - Dermatopathology
Bullous dermatomyositis with anti-NPX2 antibodies, associated with breast cancer
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Clinical</span>" "titulo" => "Solitary palmar adult xanthogranuloma" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "302" "paginaFinal" => "304" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1721 "Ancho" => 2508 "Tamanyo" => 1400191 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Histological characteristics of volar adult xanthogranuloma. (A and B) Dermal proliferation of mononucleated foamy histiocytes and Touton’s giant cells (Hematoxylin & eosin, ×40 and ×400, respectively). (C and D) Immunohistochemical stains revealing CD68 positive and CD1a negative foamy histiocytes, respectively (magnification ×200).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Laura Serra-García, Cristina Carrera, Priscila Giavedoni, Constanza Riquelme-Mc Loughlin" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Laura" "apellidos" => "Serra-García" ] 1 => array:2 [ "nombre" => "Cristina" "apellidos" => "Carrera" ] 2 => array:2 [ "nombre" => "Priscila" "apellidos" => "Giavedoni" ] 3 => array:2 [ "nombre" => "Constanza" "apellidos" => "Riquelme-Mc Loughlin" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "pt" => array:9 [ "pii" => "S2666275223002825" "doi" => "10.1016/j.abdp.2023.11.004" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "pt" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275223002825?idApp=UINPBA00008Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059623002337?idApp=UINPBA00008Z" "url" => "/03650596/0000009900000002/v2_202407221312/S0365059623002337/v2_202407221312/en/main.assets" ] "en" => array:17 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter - Dermatopathology</span>" "titulo" => "Bullous dermatomyositis with anti-NPX2 antibodies, associated with breast cancer" "tieneTextoCompleto" => true "saludo" => "<span class="elsevierStyleItalic">Dear Editor,</span>" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "305" "paginaFinal" => "307" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Francisca Reculé, Juana Benedetto, Catalina Silva-Hirschberg, Raúl Cabrera, Alex Castro" "autores" => array:5 [ 0 => array:3 [ "nombre" => "Francisca" "apellidos" => "Reculé" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Juana" "apellidos" => "Benedetto" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:4 [ "nombre" => "Catalina" "apellidos" => "Silva-Hirschberg" "email" => array:1 [ 0 => "casilvah@udd.cl" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 3 => array:3 [ "nombre" => "Raúl" "apellidos" => "Cabrera" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Alex" "apellidos" => "Castro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Department of Dermatology, Facultad de Medicina, Clínica Alemana, Universidad del Desarrollo, Santiago, Chile" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Pathology, Facultad de Medicina, Clínica Alemana, Universidad del Desarrollo, Santiago, Chile" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 3159 "Ancho" => 1508 "Tamanyo" => 888599 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">(A) 10× Hematoxylin-eosin staining; hydropic changes in the basal layer. (B and C) 10× Hematoxylin-eosin staining with marked dermal edema and bullae formation with mild lymphocytic infiltrate around superficial vessels.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Vesicle or bulla formation in Dermatomyositis (DM) is extremely rare, with approximately 68 bullous DM (BDM) cases published to date.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–7</span></a> It was first reported by Christian in 1903.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> BDM mainly affects women in the 5<span class="elsevierStyleSup">th</span>‒7<span class="elsevierStyleSup">th</span> decade. In classical DM, the male-to-female ratio is 1:2. BDM favors female presentation with a ratio of 3:1.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Blisters in BDM predominantly develop on frequently irritated areas such as extensor areas of upper extremities, knees, and trunk.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> A recent case series addresses the importance of the correlation between BDM and neoplasia.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">A 54-year-old woman with a previous diagnosis of breast cancer, treated three years ago with partial mastectomy, attended our dermatology department with a three-month history of symmetric pruriginous erythematous plaques on both thighs. She was previously treated in another hospital with a 20-day course of oral prednisolone 20 mg/day with partial response. No other treatment or vaccines were prescribed. The patient progressed with generalized skin lesions within a month. Physical examination revealed an erythematous rash with symmetrical vesicles and bullas on the neck, abdomen, arms, knees, and thighs (holster sign) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> A and B), and Gottron’s sign (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C). Oral mucosa was unaffected. Laboratory tests showed increased serum glutamic-oxaloacetic transaminase levels of 211 U/L, PCR 2.1 mg/dL, and total CK within normal limits. Extractable nuclear antigen, rheumatoid factor, rapid plasma reagin, anti-histone, anti-DNA, and antinuclear antibodies were negative. Complement C3 and C4 were normal. Histology demonstrated focal parakeratosis, hydropic changes in the basal layer with subepidermal edema and bulla formation. Mild lymphocytic infiltrate around superficial vessels with few neutrophils and dermal mucin deposition (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Direct Immunofluorescence (DIF) was only focally positive for C3 on superficial vessels. Magnetic Resonance Imaging of the extremities and neck showed mild myositis of the deltoid and trapezius muscles. The DM panel revealed positivity for anti-NPX2. A complete paraneoplastic screening was performed, which was normal.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Clinical and histopathological findings, in addition to anti-NPX2 positivity and the presence of vesicles lead us to the diagnosis of BDM. Treatment with oral tacrolimus 3 mg/day was administered with complete remission of blisters and subclinical myositis. Tacrolimus treatment was finished in March 2022 and, until this publication, there is no clinical recurrence. The patient has been followed for four years and no new neoplasia has been found.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Since clinical signs are usually non-specific in BDM, histopathology, and molecular markers become valuable diagnostic tools. The BDM histopathology commonly shows subepidermal blisters with dermal edema, mucin deposition, and superficial perivascular inflammation. Vesicles are generated by an intense inflammatory reaction and marked dermal edema.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> In about 35% of cases, DIF reveals granular deposits of immunoglobulins and complement at the dermo-epidermal junction.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> In addition, C3 and C5b-9 granular deposits can be found in vessels, probably as a nonspecific inflammatory reaction, supporting the diagnosis in our case.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,9</span></a> Differential diagnoses include: (1) Bullous erythematous lupus ‒ positive granular o linear DIF in the Basal Membrane Zone (BMZ) and anti-collagen VII antibodies, (2) Bullous pemphigoid ‒ positive linear DIF in the BMZ with anti-BP180 or BP230 antibodies, (3) Dermatitis herpetiformis ‒ DIF with granular deposits in dermal papillae, and (4) Pemphigus ‒ positive intercellular DIF and anti-desmoglein 1 and 3 antibodies.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">DM can be associated with autoimmune blister diseases. Epitope spreading has been proposed as an explanation, but their association remains unknown.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The link between DM and cancer has well known since 1960.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,6</span></a> The association with classical DM is approximately 15%‒27%.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> The association between cancer and BDM is significantly higher, ranging from 52%‒68% of patients.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,3,7</span></a> The intense inflammatory reaction found in BDM is associated with a higher paraneoplastic risk.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,6,7</span></a> There is a poorer prognosis of BDM when associated with malignancies, which can develop within the first three years after BDM diagnosis.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> This highlights the importance of an exhaustive search for neoplasms in patients diagnosed with DM, especially if BDM is present. The finding of anti-NXP2 in DM is highly related to cancer, as it was demonstrated in this report.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,7</span></a> BDM has also been associated with lung, ovarian, and esophagus tumors.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,3</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">BDM can be easily misdiagnosed. Early recognition is key to achieve a better prognosis. Patients should be closely followed up for appropriate treatment and cancer screening. Clinical examination is mandatory every 4‒6 months for at least three years and clinical images should be performed every 6‒12 months.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,11</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Herein, we report a rare clinical presentation of hypomyopathic DM in which the combination of anamnesis, physical examination, laboratory and imaging exams, and histopathologic findings played a crucial role in reaching a correct diagnosis. We emphasize that BDM should always be in the differential diagnosis of bullous diseases.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financial support</span><p id="par0045" class="elsevierStylePara elsevierViewall">None declared.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authors’ contributions</span><p id="par0050" class="elsevierStylePara elsevierViewall">Francisca Reculé: Approval of the final version of the manuscript; intellectual participation in propaedeutic and/or therapeutic management of studied cases; manuscript critical review; preparation and writing of the manuscript.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Juana Benedetto: approval of the final version of the manuscript; intellectual participation in propaedeutic and/or therapeutic management of studied cases; manuscript critical review; preparation and writing of the manuscript.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Catalina Silva-Hirschberg: Approval of the final version of the manuscript; critical literature review; manuscript critical review; preparation and writing of the manuscript.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Raúl Cabrera: Approval of the final version of the manuscript; intellectual participation in propaedeutic and/or therapeutic management of studied cases; manuscript critical review; preparation and writing of the manuscript.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Alex Castro: Approval of the final version of the manuscript; manuscript critical review; preparation and writing of the manuscript.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0075" class="elsevierStylePara elsevierViewall">None declared.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Financial support" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Authors’ contributions" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflicts of interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2022-10-16" "fechaAceptado" => "2023-01-25" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Study conducted at the Clínica Alemana de Santiago de Chile, Santiago, Chile.</p>" ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3026 "Ancho" => 1508 "Tamanyo" => 405698 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Intense erythematous rash on the abdomen and thigs associated to the presence of vesicles and bullas. (B) Magnification of vesicles and bullas on the abdomen. (C) Gottron’s sign.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 3159 "Ancho" => 1508 "Tamanyo" => 888599 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">(A) 10× Hematoxylin-eosin staining; hydropic changes in the basal layer. 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