que se leu este artigo
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Approximately 550 cases have been described in literature since its first publication.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">It is characterized by xanthogranulomatous infiltration of different tissues with numerous foam histiocytes. The disease can be very heterogeneous, ranging from indolent cases to a life-threatening multisystemic disease with possible bone, neurological, skin, hypothalamic-pituitary, pulmonary and renal infiltration.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Long bones are affected in more than 90% of the cases. They have a typical infiltration pattern which consists of symmetric osteosclerosis patches in the diaphyses without epiphyses affection.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The most frequent cutaneous manifestations are xanthelasma-type lesions that occur in 25 %–30 % of patients and which can become very deforming. Sometimes skin manifestations precede the systemic clinic.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Historically, ECD lacked effective treatments. The recent discovery that more than 60% of patients with ECD have the BRAF<span class="elsevierStyleSup">V600E</span> mutation has led to the indication of targeted therapies (MEK and BRAF inhibitors).<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a> However, when BRAF mutation is negative, there have not been prospective controlled therapeutic trials to compare treatments.</p><p id="par0030" class="elsevierStylePara elsevierViewall">We have followed up on a 55-year-old man for a decade. In 2010, at 45 years old, the patient made a consultation about cutaneous facial thickening and progressive facial deformity with difficulty in oral opening. He presented exophthalmos with yellow-orange skin, large telangiectasias, and lower eyelid big bags (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">The cutaneous manifestations were very disfiguring. After multiple facial biopsies, the diagnosis of ECD was reached after visualizing an extensive infiltration by foam macrophages (xanthic cells, CD68 +, CD163 +, S100-, CD1a−) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Initially, the patient was treated with high doses of corticosteroids (prednisone 1 mg/kg/day) and interferon. Since 2016, he has presented an increase in his basal dyspnea and a progressive elevation of acute phase reactants. It was decided to extend the study with complementary tests. Among them, splenomegaly and pulmonary infiltrate with an interstitial pattern were observed without significant bone findings. The patient presented a negative molecular study for mutations in the regions of the NRAS and BRAF genes.</p><p id="par0045" class="elsevierStylePara elsevierViewall">In 2019, it was decided to prescribe anakinra 100 mg subcutaneously daily as an off-label indication<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> due to the lack of response to the combined therapy. In case of no clinical response, anakinra could be increased to 200 mg/day.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Since then, the patient has improved progressively without requiring an increase in anakinra dose. Nowadays, the patient is asymptomatic. The skin filling has been remitted but it has required a blepharoplasty to correct the redundant skin and multiple sessions of dye-pulsed light for the treatment of facial vascular lesions (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">We have presented a rare multisystemic disease of unknown etiology, whose diagnosis and treatment continue to be a challenge today.</p><p id="par0060" class="elsevierStylePara elsevierViewall">The bone clinic, the main manifestation of the disease, is always absent. In this case, the cutaneous manifestations stand out from the beginning, even before the systemic symptoms.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Although the discovery of the involvement of the BRAF pathway in ECD has led to a revolution in its treatment, in our case it is also absent. Due to the ultra-rareness of ECD, there have not been any prospective controlled clinical trials to compare treatments.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Proinflammatory cytokines, such as IL-1, IL-6, and TNF-alpha, are strongly increased in ECD lesions. These findings suggested that inhibition of the IL-1 pathway could be a promising therapeutic area for ECD treatment.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Our experience supports the use of anakinra, an IL-1 receptor antagonist, as a therapeutic option for ECD when the BRAF mutational study is negative.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Despite the progress in understanding the underlying pathogenesis and biology of ECD, we believe that more efforts are needed in the study of the disease.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financial support</span><p id="par0085" class="elsevierStylePara elsevierViewall">None declared.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authors’ contributions</span><p id="par0090" class="elsevierStylePara elsevierViewall">Juan-Manuel Morón-Ocaña: Preparation and writing of the manuscript and critical literature review.</p><p id="par0095" class="elsevierStylePara elsevierViewall">Amalia Pérez-Gill: Approval of the final version of the manuscript and manuscript critical review.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0100" 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" => "2023-01-07" "fechaAceptado" => "2023-02-15" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Study conducted at the Dermatology team of the Hospital Universitario Virgen de Valme, Sevilla, Spain.</p>" ] ] "multimedia" => array:3 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2187 "Ancho" => 1675 "Tamanyo" => 248541 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Physical appearance 2010: cutaneous facial thickening and progressive facial deformity, exophthalmos with yellow-orange skin, large telangiectasias and lower eyelid big bags.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1640 "Ancho" => 2508 "Tamanyo" => 501462 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">(A) Hematoxylin & eosin (×20): extensive infiltration by foam macrophages. (B) IHQ (×10): xantic cells CD68+. (C) IHQ (×10); xantic cells S100−, CD1a−.</p>" ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1787 "Ancho" => 1508 "Tamanyo" => 150844 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Physical appearance 2020: The skin infiltration has remitted after anakinra, blepharoplasty and dye-pulsed light.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:6 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Erdheim-Chester disease: a systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. 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