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however&#44; anti-thyroglobulin antibody &#40;209&#46;2&#8239;IU&#47;mL&#59; normal &#60;28&#41; and anti-thyroid peroxidase antibody &#40;269&#46;1&#8239;IU&#47;mL&#44; normal &#60;16&#41; were elevated&#46; Thyroid Stimulating Hormone &#40;TSH&#41;&#44; TSH receptor antibody&#44; and free T3 and T4 thyroid hormones were all within normal limits&#46; Histological examination revealed necrobiotic changes of collagen in the dermis&#44; surrounded by granulomatous inflammatory reactions composed of lymphocytes&#44; histiocytes&#44; and multinucleated giant cells &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A&#41;&#46; Of note&#44; lymphoid aggregates were observed at the periphery of the degenerated collagen in the lower dermis&#46; Immunohistological examination showed intense expression of CD3&#43; T-cells &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>B&#41; and CD20&#43; B-cells &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>C&#41;&#46; High endothelial venules-associated pNAd &#40;MECA-79&#41; epitopes were observed within the lymphoid aggregates &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>D&#41;&#44; and CXCL13 positive cells were scattered within the lymphoid clusters&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">The most common disease associated with Necrobiosis Lipoidica &#40;NL&#41; is diabetes mellitus&#44; which was observed in 43&#37; of the patients with NL&#44; while thyroid disorders were detected in 15&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> In the present case&#44; NL and thyroid disease developed almost simultaneously&#46; However&#44; hormonal effects on the development of NL were unexpected because thyroid hormone levels were normal&#46; Our patient developed NL as an initial lesion on the site of an old burn scar&#44; which she received 40 years previously&#44; then increased in number on the nearby areas unassociated with a burned scar&#46; Burned sites undergo a reduction of immunity and thus become immunocompromised districts&#44; where the immune behavior is compromised forever&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Alternatively&#44; NL occurred on the old scar fortuitously&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Another unique point in the present case is the histological feature of lymphoid follicles in the biopsied specimen&#46; Lymphoid follicle-like structures were reported in the lesional skin of NL at a frequency of 11&#37; &#40;34 of 310 cases&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Ectopic lymphoid neogenesis is associated with the development of high endothelial venules and is mediated by homing chemokines such as CXCL13&#46; IL-17 and IL-23 are associated with the development of lymphoid follicles&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> IL-17 causes induction of the lymphoid chemokine&#44; CXCL13&#46; In the present case&#44; CD20 was detected in the center of the lymphoid follicles&#44; whereas CD3 was observed diffusely&#46; pNAd-positive cells were scattered within the lymphoid follicles&#46; Recent studies have shown that IL-17 was abundantly detected in NL&#44; which may induce granuloma formation by suppressing regulatory T-cells&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Further studies are needed to clarify the significance of ectopic lymphoid follicles in the pathogenesis of NL&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financial support</span><p id="par0020" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authors&#39; contributions</span><p id="par0025" class="elsevierStylePara elsevierViewall">Shohei Igari&#58; Designed the study&#59; performed the study and contributed to analysis and interpretation of data&#59; wrote the drafting the manuscript&#59; approved the final version of the manuscript&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Mayu Sato&#58; Performed the study and contributed to analysis and interpretation of data&#59; approved the final version of the manuscript&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Toshiyuki Yamamoto&#58; Designed the study&#59; revised the manuscript for important intellectual content&#59; approved the final version of the manuscript&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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Case Letter
Necrobiosis lipoidica arising on an old burn scar in a patient with Hashimoto's thyroiditis
Shohei Igari
Corresponding author
shohey19@fmu.ac.jp

Corresponding author.
, Mayu Sato, Toshiyuki Yamamoto
Department of Dermatology, Fukushima Medical University, Fukushima, Japan
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">A 58-year-old female visited our department&#44; complaining of asymptomatic skin lesions on the lower legs&#44; which had appeared two years previously&#46; She did not have diabetes&#59; however&#44; she had been diagnosed as having a goiter at almost the same time as when the skin lesions began and were under follow-up&#46; Physical examination showed several well-circumscribed waxy brownish infiltrated plaques with elevated borders on the bilateral shins &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A and <a class="elsevierStyleCrossRef" href="#fig0005">1</a>B&#41;&#46; Initial lesion arose on a burn scar&#44; which had originally been caused by a Japanese electric foot warmer&#44; that is used in the bed in winter&#46; Thereafter&#44; similar lesions were increased in number in the surrounding areas and spread to another lower leg&#46; Laboratory examination showed normal liver and renal function&#59; however&#44; anti-thyroglobulin antibody &#40;209&#46;2&#8239;IU&#47;mL&#59; normal &#60;28&#41; and anti-thyroid peroxidase antibody &#40;269&#46;1&#8239;IU&#47;mL&#44; normal &#60;16&#41; were elevated&#46; Thyroid Stimulating Hormone &#40;TSH&#41;&#44; TSH receptor antibody&#44; and free T3 and T4 thyroid hormones were all within normal limits&#46; Histological examination revealed necrobiotic changes of collagen in the dermis&#44; surrounded by granulomatous inflammatory reactions composed of lymphocytes&#44; histiocytes&#44; and multinucleated giant cells &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A&#41;&#46; Of note&#44; lymphoid aggregates were observed at the periphery of the degenerated collagen in the lower dermis&#46; Immunohistological examination showed intense expression of CD3&#43; T-cells &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>B&#41; and CD20&#43; B-cells &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>C&#41;&#46; High endothelial venules-associated pNAd &#40;MECA-79&#41; epitopes were observed within the lymphoid aggregates &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>D&#41;&#44; and CXCL13 positive cells were scattered within the lymphoid clusters&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">The most common disease associated with Necrobiosis Lipoidica &#40;NL&#41; is diabetes mellitus&#44; which was observed in 43&#37; of the patients with NL&#44; while thyroid disorders were detected in 15&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> In the present case&#44; NL and thyroid disease developed almost simultaneously&#46; However&#44; hormonal effects on the development of NL were unexpected because thyroid hormone levels were normal&#46; Our patient developed NL as an initial lesion on the site of an old burn scar&#44; which she received 40 years previously&#44; then increased in number on the nearby areas unassociated with a burned scar&#46; Burned sites undergo a reduction of immunity and thus become immunocompromised districts&#44; where the immune behavior is compromised forever&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Alternatively&#44; NL occurred on the old scar fortuitously&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Another unique point in the present case is the histological feature of lymphoid follicles in the biopsied specimen&#46; Lymphoid follicle-like structures were reported in the lesional skin of NL at a frequency of 11&#37; &#40;34 of 310 cases&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Ectopic lymphoid neogenesis is associated with the development of high endothelial venules and is mediated by homing chemokines such as CXCL13&#46; IL-17 and IL-23 are associated with the development of lymphoid follicles&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> IL-17 causes induction of the lymphoid chemokine&#44; CXCL13&#46; In the present case&#44; CD20 was detected in the center of the lymphoid follicles&#44; whereas CD3 was observed diffusely&#46; pNAd-positive cells were scattered within the lymphoid follicles&#46; Recent studies have shown that IL-17 was abundantly detected in NL&#44; which may induce granuloma formation by suppressing regulatory T-cells&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Further studies are needed to clarify the significance of ectopic lymphoid follicles in the pathogenesis of NL&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financial support</span><p id="par0020" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authors&#39; contributions</span><p id="par0025" class="elsevierStylePara elsevierViewall">Shohei Igari&#58; Designed the study&#59; performed the study and contributed to analysis and interpretation of data&#59; wrote the drafting the manuscript&#59; approved the final version of the manuscript&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Mayu Sato&#58; Performed the study and contributed to analysis and interpretation of data&#59; approved the final version of the manuscript&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Toshiyuki Yamamoto&#58; Designed the study&#59; revised the manuscript for important intellectual content&#59; approved the final version of the manuscript&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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ISSN: 03650596
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