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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Association of sarcoidosis and autoimmune thyroiditis is rare&#46; We report a case of cutaneous sarcoid surrounded by livedo on the lower extremities in a patient with Hashimoto&#39;s thyroiditis&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 72-year-old female visited the Department of Dermatology of Hoshi General Hospital&#44; complaining of asymptomatic reddish eruptions on the lower extremities which appeared six months previously&#46; She had Hashimoto&#39;s thyroiditis for several years&#44; but had been followed without medications&#46; Physical examination showed multiple reddish&#44; infiltrative round and irregular-shaped&#44; up to 4-cm sized plaques on the anterior aspects of the bilateral thighs and lower legs &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>a&#41;&#46; The erythematous plaques coalesced on the left thigh&#44; and livedo was observed in the surroundings of the plaques on the thighs&#46; Laboratory examination showed normal levels of angiotensin-converting enzyme &#40;ACE&#41; &#40;13&#46;6<span class="elsevierStyleHsp" style=""></span>U&#47;L&#44; normal&#58; 7&#8211;25&#41;&#46; Anti-thyroglobulin antibody showed high titers &#40;86&#46;8<span class="elsevierStyleHsp" style=""></span>IU&#47;ml&#59; normal &#60;28&#41;&#44; however&#44; anti-thyroid peroxidase antibody&#44; thyroid stimulating hormone&#44; free T3 and T4 levels were within normal ranges&#46; Chest X-ray did not reveal bilateral hilar lymphadenopathy&#46; Computed tomography revealed a few lymph nodes within normal ranges and thyroid nodule&#46; Ophthalmological examination denied uveitis&#46; A tuberculin test revealed positive erythematous reaction sized 2-cm without induration&#46; A skin biopsy taken from reddish plaque showed non-caseating granulomas with epithelioid cells throughout the dermis &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>b&#41;&#46; Periodic acid-Schiff &#40;PAS&#41; and Ziehl&#8211;Neelsen staining did not detect bacilli&#46; Immunohistochemistry revealed a number of CD68-positive macrophages in the lesional skin&#46; Tumor necrosis factor-&#945; &#40;TNF-&#945;&#41; and interleukin-17 &#40;IL-17&#41; positive cells were also detected densely &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>c and d&#41;&#46; Elastica van Gieson stain showed that multiple sarcoidal granulomas were located around the vessels&#44; but without fibrinoid degeneration&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Autoimmune thyroiditis is sometimes seen in association with sarcoidosis&#44;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> and to date&#44; several cases of co-occurrence of sarcoidosis and Hashimoto&#39;s thyroiditis have been reported&#46; Isernet et al&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a> reported that 10 out of 348 patients with sarcoidosis had autoimmune thyroiditis&#44; and sarcoidosis preceded autoimmune thyroiditis in 9 cases&#46; The diagnosis of autoimmune thyroiditis was made when sarcoidosis was in remission&#46; Papadopoulos et al&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a> reported that 13 patients had thyroid autoimmunity &#40;6 with Hashimoto&#39;s thyroiditis&#44; 2 with Graves&#8217; disease and 5 with isolated positive thyroid serology&#41; among a series of 78 patients with sarcoidosis&#46; Nakamura et al&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a> found 7 cases of Hashimoto&#39;s thyroiditis in a series of 62 patients with pulmonary sarcoidosis&#46; Unfortunately&#44; an open biopsy of thyroid nodule was not carried out to differentiate thyroid sarcoidosis in the present case&#46; At present&#44; sarcoidal lesions were not detected in other organs&#44; <span class="elsevierStyleItalic">i&#46;e&#46;</span> lung or eyes&#46; Moreover&#44; a tuberculin test revealed positive reaction&#46; Therefore&#44; we consider that the patient developed cutaneous sarcoid only&#59; however&#44; we will carefully follow-up this patient whether symptoms of systemic sarcoidosis will appear in the future&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Macrophages play an important role in sarcoidal granuloma formation <span class="elsevierStyleItalic">via</span> several cytokines such as TNF-&#945; and IL-1&#946;&#46; Several recent studies have reported the effectiveness of TNF-&#945; inhibition for sarcoidosis&#46; Our studies showed a number of CD163-positive macrophages surrounding the degenerated collagen in the dermis&#46; In addition&#44; strong expression of IL-17 and TNF-&#945; was detected in the lesional skin of sarcoidosis&#46; TNF-&#945; activates Th17 cells leading IL-17 production&#44; and recent studies have shown that IL-17 was abundantly detected in sarcoidal lesions&#44; suggesting that Th17 cells induce granuloma formation by suppressing regulatory T-cells&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a> Recent findings suggest an important etiologic role of <span class="elsevierStyleItalic">Propionibacterium acnes</span> &#40;<span class="elsevierStyleItalic">P&#46; acnes</span>&#41; in sarcoidosis&#46; <span class="elsevierStyleItalic">P&#46; acnes</span> induces IL-17 and interferon-&#947;&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">6</span></a> and is thus implicated to play a pathogenic role in sarcoidosis <span class="elsevierStyleItalic">via</span> Th1&#47;Th17 cytokines&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Finally&#44; livedo was seen around sarcoidal plaques on the bilateral thigh&#46; To date&#44; only a few cases have been presented with livedo in association with sarcoidosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">7&#8211;9</span></a> A biopsy was taken from the sarcoidal plaque&#44; but not from the surrounding livedo&#46; However&#44; histological examination showed granulomas around the vessels&#44; which may induce livedo&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Ethical disclosures</span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Protection of human subjects and animals in research</span><p id="par0030" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this investigation&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Confidentiality of data</span><p id="par0035" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Right to privacy and informed consent</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors have obtained the written informed consent of the patients or subjects mentioned in the article&#46; The corresponding author is in possession of this document&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conflict of interest</span><p id="par0045" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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Case and Research Letter
Cutaneous Sarcoid with Livedoid Changes in a Patient with Hashimoto's Thyroiditis
Sarcoidosis cutánea con cambios livedoides en un paciente con tiroiditis de Hashimoto
T. Yamamotoa,
Autor para correspondencia
toyamade@fmu.ac.jp

Corresponding author.
, H. Okabeb
a Department of Dermatology, Fukushima Medical University, Fukushima, Japan
b Department of Dermatology, Hoshi General Hospital, Fukushima, Japan
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Association of sarcoidosis and autoimmune thyroiditis is rare&#46; We report a case of cutaneous sarcoid surrounded by livedo on the lower extremities in a patient with Hashimoto&#39;s thyroiditis&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 72-year-old female visited the Department of Dermatology of Hoshi General Hospital&#44; complaining of asymptomatic reddish eruptions on the lower extremities which appeared six months previously&#46; She had Hashimoto&#39;s thyroiditis for several years&#44; but had been followed without medications&#46; Physical examination showed multiple reddish&#44; infiltrative round and irregular-shaped&#44; up to 4-cm sized plaques on the anterior aspects of the bilateral thighs and lower legs &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>a&#41;&#46; The erythematous plaques coalesced on the left thigh&#44; and livedo was observed in the surroundings of the plaques on the thighs&#46; Laboratory examination showed normal levels of angiotensin-converting enzyme &#40;ACE&#41; &#40;13&#46;6<span class="elsevierStyleHsp" style=""></span>U&#47;L&#44; normal&#58; 7&#8211;25&#41;&#46; Anti-thyroglobulin antibody showed high titers &#40;86&#46;8<span class="elsevierStyleHsp" style=""></span>IU&#47;ml&#59; normal &#60;28&#41;&#44; however&#44; anti-thyroid peroxidase antibody&#44; thyroid stimulating hormone&#44; free T3 and T4 levels were within normal ranges&#46; Chest X-ray did not reveal bilateral hilar lymphadenopathy&#46; Computed tomography revealed a few lymph nodes within normal ranges and thyroid nodule&#46; Ophthalmological examination denied uveitis&#46; A tuberculin test revealed positive erythematous reaction sized 2-cm without induration&#46; A skin biopsy taken from reddish plaque showed non-caseating granulomas with epithelioid cells throughout the dermis &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>b&#41;&#46; Periodic acid-Schiff &#40;PAS&#41; and Ziehl&#8211;Neelsen staining did not detect bacilli&#46; Immunohistochemistry revealed a number of CD68-positive macrophages in the lesional skin&#46; Tumor necrosis factor-&#945; &#40;TNF-&#945;&#41; and interleukin-17 &#40;IL-17&#41; positive cells were also detected densely &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>c and d&#41;&#46; Elastica van Gieson stain showed that multiple sarcoidal granulomas were located around the vessels&#44; but without fibrinoid degeneration&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Autoimmune thyroiditis is sometimes seen in association with sarcoidosis&#44;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> and to date&#44; several cases of co-occurrence of sarcoidosis and Hashimoto&#39;s thyroiditis have been reported&#46; Isernet et al&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a> reported that 10 out of 348 patients with sarcoidosis had autoimmune thyroiditis&#44; and sarcoidosis preceded autoimmune thyroiditis in 9 cases&#46; The diagnosis of autoimmune thyroiditis was made when sarcoidosis was in remission&#46; Papadopoulos et al&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a> reported that 13 patients had thyroid autoimmunity &#40;6 with Hashimoto&#39;s thyroiditis&#44; 2 with Graves&#8217; disease and 5 with isolated positive thyroid serology&#41; among a series of 78 patients with sarcoidosis&#46; Nakamura et al&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a> found 7 cases of Hashimoto&#39;s thyroiditis in a series of 62 patients with pulmonary sarcoidosis&#46; Unfortunately&#44; an open biopsy of thyroid nodule was not carried out to differentiate thyroid sarcoidosis in the present case&#46; At present&#44; sarcoidal lesions were not detected in other organs&#44; <span class="elsevierStyleItalic">i&#46;e&#46;</span> lung or eyes&#46; Moreover&#44; a tuberculin test revealed positive reaction&#46; Therefore&#44; we consider that the patient developed cutaneous sarcoid only&#59; however&#44; we will carefully follow-up this patient whether symptoms of systemic sarcoidosis will appear in the future&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Macrophages play an important role in sarcoidal granuloma formation <span class="elsevierStyleItalic">via</span> several cytokines such as TNF-&#945; and IL-1&#946;&#46; Several recent studies have reported the effectiveness of TNF-&#945; inhibition for sarcoidosis&#46; Our studies showed a number of CD163-positive macrophages surrounding the degenerated collagen in the dermis&#46; In addition&#44; strong expression of IL-17 and TNF-&#945; was detected in the lesional skin of sarcoidosis&#46; TNF-&#945; activates Th17 cells leading IL-17 production&#44; and recent studies have shown that IL-17 was abundantly detected in sarcoidal lesions&#44; suggesting that Th17 cells induce granuloma formation by suppressing regulatory T-cells&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a> Recent findings suggest an important etiologic role of <span class="elsevierStyleItalic">Propionibacterium acnes</span> &#40;<span class="elsevierStyleItalic">P&#46; acnes</span>&#41; in sarcoidosis&#46; <span class="elsevierStyleItalic">P&#46; acnes</span> induces IL-17 and interferon-&#947;&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">6</span></a> and is thus implicated to play a pathogenic role in sarcoidosis <span class="elsevierStyleItalic">via</span> Th1&#47;Th17 cytokines&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Finally&#44; livedo was seen around sarcoidal plaques on the bilateral thigh&#46; To date&#44; only a few cases have been presented with livedo in association with sarcoidosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">7&#8211;9</span></a> A biopsy was taken from the sarcoidal plaque&#44; but not from the surrounding livedo&#46; However&#44; histological examination showed granulomas around the vessels&#44; which may induce livedo&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Ethical disclosures</span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Protection of human subjects and animals in research</span><p id="par0030" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this investigation&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Confidentiality of data</span><p id="par0035" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Right to privacy and informed consent</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors have obtained the written informed consent of the patients or subjects mentioned in the article&#46; The corresponding author is in possession of this document&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conflict of interest</span><p id="par0045" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">&#40;a&#41; Reddish plaques on the thigh along with livedoid changes&#46; &#40;b&#41; Histological features showing sarcoidal granuloma&#44; which are immunoreactive for TNF-&#945; &#40;c&#41; and IL-17 &#40;d&#41; &#40;original magnification&#58; b&#59; &#215;400&#44; c&#59; &#215;200&#44; d&#59; &#215;200&#41;&#46;</p>"
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