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geophilic organisms with a high prevalence in humid areas of tropical and subtropical climates&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a> The most frequently affected sites are the lower limbs due to a traumatic mechanism&#44; through the inoculation of hyphae and fungal conidia into the host&#8217;s skin&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;4</span></a> Once installed in the tissue&#44; the fungus adheres to the epithelial cells and differentiates into structures called muriform&#44; fumagoid&#44; or sclerotic cells&#44; also known as Medlar bodies &#40;MB&#41;&#44; which resist destruction by the host&#39;s effector cells&#44; favoring the progression of the infection&#46; The cutaneous lesions are polymorphic&#44; including nodules&#44; plaques&#44; tumors&#44; and scars&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;4</span></a> The diagnosis of CBM is confirmed by the detection of MB&#44; pathognomonic of CBM&#44; in direct mycological and histopathological examination&#44; regardless of the species involved &#40;<a class="elsevierStyleCrossRefs" href="#fig0010">Figs&#46; 2 and 3</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a></p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Reports of dematiaceous hyphae found in association with MB have been described for decades&#44; primarily by Borelli&#46; The morphological aspect that the fungal structures acquire was called BS&#44; and its finding was initially associated with the more pathogenic species of this mycosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#8211;8</span></a> Subsequently&#44; this finding was associated with the species that were more resistant to therapy&#44; being indicative of low response to classic treatments&#44; requiring associations&#44; dose adjustments&#44; or surgical approaches in many cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;6&#44;7</span></a> These structures are evident in both direct mycological and histopathological examinations&#44; as seen in the present case &#40;<a class="elsevierStyleCrossRefs" href="#fig0020">Figs&#46; 4 and 5</a>&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">In studies on CBM immunology&#44; it was observed that the fungi are able to regulate the host&#39;s inflammatory response&#44; preventing the inflammatory process and contributing to the adaptation and opportunism process&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> MBs can alter the gene expression pattern of macrophages&#44; resulting in the histopathological characteristics observed in CBM with granulomatous inflammatory infiltrates&#44; sometimes suppurative and with the presence of micro-abscesses&#46; The presence of hyphae and muriform cells in the tissues increases the levels of the inflammatory cytokines TNF-&#945; &#40;tumor necrosis factor-alpha&#41;&#44; IL-1&#946; &#40;interleukin 1-beta&#41;&#44; and IL-6 &#40;interleukin-6&#41;&#44; increasing disease duration and the pathogen persistence in the tissue&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> This uncontrolled and chronic immune response does not provide protection for the host against the fungus and ends up leading to the maintenance of the infection&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> However&#44; studies that correlate the pathophysiology related to BS and its immune response are still lacking in the literature&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The understanding of these findings becomes of the utmost importance for the treatment of CBM&#44; which is considered a challenge&#44; especially in the most exuberant and severe clinical forms&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> The treatment of CBM is associated with low cure rates and high chances of recurrence&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a> Long periods of therapy with antifungals are required&#44; which can be associated with surgery&#44; cryotherapy&#44; thermotherapy&#44; and immunotherapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2&#44;10</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">These data lead us to understand that the parasite&#47;host binomial balance is affected by interference on both sides&#44; which may favor the emergence of BS and would possibly act to make the disease chronic and hinder therapy&#46; With the advancement of the use of immunomodulatory drugs&#44; the possibility of finding these structures increases&#46; Future studies on the clinical presentations and laboratory&#44; and therapeutic expressions in these cases may help to better understand the disease and its management&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Financial support</span><p id="par0035" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Authors&#8217; contributions</span><p id="par0040" class="elsevierStylePara elsevierViewall">Gustavo de S&#225; Menezes Carvalho&#58; Drafting and editing of the manuscript&#59; collection&#44; analysis&#44; and interpretation of data&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Karina Baruel de Camargo Votto Calbucci&#58; Drafting and editing of the manuscript&#59; collection&#44; analysis&#44; and interpretation of data&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Rute Facchini Lellis&#58; Collection&#44; analysis and interpretation of data&#59; effective participation in research orientation&#59; critical review of the literature&#59; critical review of the manuscript&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">John Verrinder Veasey&#58; Approval of the final version of the manuscript&#59; design and planning of the study&#59; drafting and editing of the manuscript&#59; collection&#44; analysis and interpretation of data&#59; effective participation in research orientation&#59; critical review of the literature&#59; critical review of the manuscript&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conflicts of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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Images in Dermatology
Presence of hyphae in chromoblastomycosis examinations: an enigma to be solved
Gustavo de Sá Menezes Carvalhoa,
Autor para correspondência
gustavo.carvalho@msn.com

Corresponding author.
, Karina Baruel de Camargo Votto Calbuccia, Rute Facchini Lellisb, John Verrinder Veaseya
a Dermatology Clinic, Santa Casa de Misericórdia, São Paulo, SP, Brazil
b Pathology Laboratory, Santa Casa de Misericórdia, São Paulo, SP, Brazil
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The anatomopathological examination showed MB&#44; some associated with dematiaceous hyphae&#44; which received the name of &#8220;Borelli&#39;s spiders&#8221; &#40;BS&#41;&#46; These findings confirmed the diagnosis of chromoblastomycosis &#40;CBM&#41;&#44; and then treatment with itraconazole &#40;200&#160;mg&#47;day for six months&#41; was started&#44; with no significant improvement of the lesions&#59; therefore&#44; it was necessary to combine other therapies &#40;cryotherapy and surgical excision&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Discussion</span><p id="par0010" class="elsevierStylePara elsevierViewall">CBM is a type of mycosis with chronic evolution that affects the skin and subcutaneous tissue&#44; caused by dematiaceous filamentous fungi&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> Its main causative agents are <span class="elsevierStyleItalic">Fonsecaea pedrosoi</span> and <span class="elsevierStyleItalic">Phialophora verrucosa</span>&#44; geophilic organisms with a high prevalence in humid areas of tropical and subtropical climates&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a> The most frequently affected sites are the lower limbs due to a traumatic mechanism&#44; through the inoculation of hyphae and fungal conidia into the host&#8217;s skin&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;4</span></a> Once installed in the tissue&#44; the fungus adheres to the epithelial cells and differentiates into structures called muriform&#44; fumagoid&#44; or sclerotic cells&#44; also known as Medlar bodies &#40;MB&#41;&#44; which resist destruction by the host&#39;s effector cells&#44; favoring the progression of the infection&#46; The cutaneous lesions are polymorphic&#44; including nodules&#44; plaques&#44; tumors&#44; and scars&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;4</span></a> The diagnosis of CBM is confirmed by the detection of MB&#44; pathognomonic of CBM&#44; in direct mycological and histopathological examination&#44; regardless of the species involved &#40;<a class="elsevierStyleCrossRefs" href="#fig0010">Figs&#46; 2 and 3</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a></p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Reports of dematiaceous hyphae found in association with MB have been described for decades&#44; primarily by Borelli&#46; The morphological aspect that the fungal structures acquire was called BS&#44; and its finding was initially associated with the more pathogenic species of this mycosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#8211;8</span></a> Subsequently&#44; this finding was associated with the species that were more resistant to therapy&#44; being indicative of low response to classic treatments&#44; requiring associations&#44; dose adjustments&#44; or surgical approaches in many cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;6&#44;7</span></a> These structures are evident in both direct mycological and histopathological examinations&#44; as seen in the present case &#40;<a class="elsevierStyleCrossRefs" href="#fig0020">Figs&#46; 4 and 5</a>&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">In studies on CBM immunology&#44; it was observed that the fungi are able to regulate the host&#39;s inflammatory response&#44; preventing the inflammatory process and contributing to the adaptation and opportunism process&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> MBs can alter the gene expression pattern of macrophages&#44; resulting in the histopathological characteristics observed in CBM with granulomatous inflammatory infiltrates&#44; sometimes suppurative and with the presence of micro-abscesses&#46; The presence of hyphae and muriform cells in the tissues increases the levels of the inflammatory cytokines TNF-&#945; &#40;tumor necrosis factor-alpha&#41;&#44; IL-1&#946; &#40;interleukin 1-beta&#41;&#44; and IL-6 &#40;interleukin-6&#41;&#44; increasing disease duration and the pathogen persistence in the tissue&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> This uncontrolled and chronic immune response does not provide protection for the host against the fungus and ends up leading to the maintenance of the infection&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> However&#44; studies that correlate the pathophysiology related to BS and its immune response are still lacking in the literature&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The understanding of these findings becomes of the utmost importance for the treatment of CBM&#44; which is considered a challenge&#44; especially in the most exuberant and severe clinical forms&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> The treatment of CBM is associated with low cure rates and high chances of recurrence&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a> Long periods of therapy with antifungals are required&#44; which can be associated with surgery&#44; cryotherapy&#44; thermotherapy&#44; and immunotherapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2&#44;10</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">These data lead us to understand that the parasite&#47;host binomial balance is affected by interference on both sides&#44; which may favor the emergence of BS and would possibly act to make the disease chronic and hinder therapy&#46; With the advancement of the use of immunomodulatory drugs&#44; the possibility of finding these structures increases&#46; Future studies on the clinical presentations and laboratory&#44; and therapeutic expressions in these cases may help to better understand the disease and its management&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Financial support</span><p id="par0035" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Authors&#8217; contributions</span><p id="par0040" class="elsevierStylePara elsevierViewall">Gustavo de S&#225; Menezes Carvalho&#58; Drafting and editing of the manuscript&#59; collection&#44; analysis&#44; and interpretation of data&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Karina Baruel de Camargo Votto Calbucci&#58; Drafting and editing of the manuscript&#59; collection&#44; analysis&#44; and interpretation of data&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Rute Facchini Lellis&#58; Collection&#44; analysis and interpretation of data&#59; effective participation in research orientation&#59; critical review of the literature&#59; critical review of the manuscript&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">John Verrinder Veasey&#58; Approval of the final version of the manuscript&#59; design and planning of the study&#59; drafting and editing of the manuscript&#59; collection&#44; analysis and interpretation of data&#59; effective participation in research orientation&#59; critical review of the literature&#59; critical review of the manuscript&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conflicts of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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ISSN: 03650596
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