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of patients and which can become very deforming&#46; Sometimes skin manifestations precede the systemic clinic&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Historically&#44; ECD lacked effective treatments&#46; The recent discovery that more than 60&#37; of patients with ECD have the BRAF<span class="elsevierStyleSup">V600E</span> mutation has led to the indication of targeted therapies &#40;MEK and BRAF inhibitors&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> However&#44; when BRAF mutation is negative&#44; there have not been prospective controlled therapeutic trials to compare treatments&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">We have followed up on a 55-year-old man for a decade&#46; In 2010&#44; at 45 years old&#44; the patient made a consultation about cutaneous facial thickening and progressive facial deformity with difficulty in oral opening&#46; He presented exophthalmos with yellow-orange skin&#44; large telangiectasias&#44; and lower eyelid big bags &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">The cutaneous manifestations were very disfiguring&#46; After multiple facial biopsies&#44; the diagnosis of ECD was reached after visualizing an extensive infiltration by foam macrophages &#40;xanthic cells&#44; CD68 &#43;&#44; CD163 &#43;&#44; S100-&#44; CD1a&#8722;&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Initially&#44; the patient was treated with high doses of corticosteroids &#40;prednisone 1&#8239;mg&#47;kg&#47;day&#41; and interferon&#46; Since 2016&#44; he has presented an increase in his basal dyspnea and a progressive elevation of acute phase reactants&#46; It was decided to extend the study with complementary tests&#46; Among them&#44; splenomegaly and pulmonary infiltrate with an interstitial pattern were observed without significant bone findings&#46; The patient presented a negative molecular study for mutations in the regions of the NRAS and BRAF genes&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">In 2019&#44; it was decided to prescribe anakinra 100&#8239;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&#46; In case of no clinical response&#44; anakinra could be increased to 200&#8239;mg&#47;day&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Since then&#44; the patient has improved progressively without requiring an increase in anakinra dose&#46; Nowadays&#44; the patient is asymptomatic&#46; 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 &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">We have presented a rare multisystemic disease of unknown etiology&#44; whose diagnosis and treatment continue to be a challenge today&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The bone clinic&#44; the main manifestation of the disease&#44; is always absent&#46; In this case&#44; the cutaneous manifestations stand out from the beginning&#44; even before the systemic symptoms&#46;</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&#44; in our case it is also absent&#46; Due to the ultra-rareness of ECD&#44; there have not been any prospective controlled clinical trials to compare treatments&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Proinflammatory cytokines&#44; such as IL-1&#44; IL-6&#44; and TNF-alpha&#44; are strongly increased in ECD lesions&#46; These findings suggested that inhibition of the IL-1 pathway could be a promising therapeutic area for ECD treatment&#46;<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&#44; an IL-1 receptor antagonist&#44; as a therapeutic option for ECD when the BRAF mutational study is negative&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Despite the progress in understanding the underlying pathogenesis and biology of ECD&#44; we believe that more efforts are needed in the study of the disease&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financial support</span><p id="par0085" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authors&#8217; contributions</span><p id="par0090" class="elsevierStylePara elsevierViewall">Juan-Manuel Mor&#243;n-Oca&#241;a&#58; Preparation and writing of the manuscript and critical literature review&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Amalia P&#233;rez-Gill&#58; Approval of the final version of the manuscript and manuscript critical review&#46;</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&#46;</p></span></span>"
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Letter - Clinical
Erdheim-Chester disease BRAF (-) Diagnosis through cutaneous manifestations and good response with anakinra treatment
Juan-Manuel Morón-Ocaña
Corresponding author
, Amalia Pérez-Gil
Dermatology, Hospital Universitario Virgen de Valme, Sevilla, Spain
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    "titulo" => "Erdheim-Chester disease BRAF &#40;-&#41; Diagnosis through cutaneous manifestations and good response with anakinra treatment"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Erdheim-Chester disease &#40;ECD&#41; is a very rare non-Largerhans systemic histiocytosis of unknown origin&#46; Approximately 550 cases have been described in literature since its first publication&#46;<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&#46; The disease can be very heterogeneous&#44; ranging from indolent cases to a life-threatening multisystemic disease with possible bone&#44; neurological&#44; skin&#44; hypothalamic-pituitary&#44; pulmonary and renal infiltration&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Long bones are affected in more than 90&#37; of the cases&#46; They have a typical infiltration pattern which consists of symmetric osteosclerosis patches in the diaphyses without epiphyses affection&#46;<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 &#37;&#8211;30 &#37; of patients and which can become very deforming&#46; Sometimes skin manifestations precede the systemic clinic&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Historically&#44; ECD lacked effective treatments&#46; The recent discovery that more than 60&#37; of patients with ECD have the BRAF<span class="elsevierStyleSup">V600E</span> mutation has led to the indication of targeted therapies &#40;MEK and BRAF inhibitors&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> However&#44; when BRAF mutation is negative&#44; there have not been prospective controlled therapeutic trials to compare treatments&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">We have followed up on a 55-year-old man for a decade&#46; In 2010&#44; at 45 years old&#44; the patient made a consultation about cutaneous facial thickening and progressive facial deformity with difficulty in oral opening&#46; He presented exophthalmos with yellow-orange skin&#44; large telangiectasias&#44; and lower eyelid big bags &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">The cutaneous manifestations were very disfiguring&#46; After multiple facial biopsies&#44; the diagnosis of ECD was reached after visualizing an extensive infiltration by foam macrophages &#40;xanthic cells&#44; CD68 &#43;&#44; CD163 &#43;&#44; S100-&#44; CD1a&#8722;&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Initially&#44; the patient was treated with high doses of corticosteroids &#40;prednisone 1&#8239;mg&#47;kg&#47;day&#41; and interferon&#46; Since 2016&#44; he has presented an increase in his basal dyspnea and a progressive elevation of acute phase reactants&#46; It was decided to extend the study with complementary tests&#46; Among them&#44; splenomegaly and pulmonary infiltrate with an interstitial pattern were observed without significant bone findings&#46; The patient presented a negative molecular study for mutations in the regions of the NRAS and BRAF genes&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">In 2019&#44; it was decided to prescribe anakinra 100&#8239;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&#46; In case of no clinical response&#44; anakinra could be increased to 200&#8239;mg&#47;day&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Since then&#44; the patient has improved progressively without requiring an increase in anakinra dose&#46; Nowadays&#44; the patient is asymptomatic&#46; 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 &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">We have presented a rare multisystemic disease of unknown etiology&#44; whose diagnosis and treatment continue to be a challenge today&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The bone clinic&#44; the main manifestation of the disease&#44; is always absent&#46; In this case&#44; the cutaneous manifestations stand out from the beginning&#44; even before the systemic symptoms&#46;</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&#44; in our case it is also absent&#46; Due to the ultra-rareness of ECD&#44; there have not been any prospective controlled clinical trials to compare treatments&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Proinflammatory cytokines&#44; such as IL-1&#44; IL-6&#44; and TNF-alpha&#44; are strongly increased in ECD lesions&#46; These findings suggested that inhibition of the IL-1 pathway could be a promising therapeutic area for ECD treatment&#46;<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&#44; an IL-1 receptor antagonist&#44; as a therapeutic option for ECD when the BRAF mutational study is negative&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Despite the progress in understanding the underlying pathogenesis and biology of ECD&#44; we believe that more efforts are needed in the study of the disease&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financial support</span><p id="par0085" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authors&#8217; contributions</span><p id="par0090" class="elsevierStylePara elsevierViewall">Juan-Manuel Mor&#243;n-Oca&#241;a&#58; Preparation and writing of the manuscript and critical literature review&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Amalia P&#233;rez-Gill&#58; Approval of the final version of the manuscript and manuscript critical review&#46;</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&#46;</p></span></span>"
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Article information
ISSN: 03650596
Original language: English
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