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1</a>&#41;&#46; At the time of consultation&#44; this lesion had two months of evolution and since then&#44; more nodular lesions have appeared on both limbs&#46; She also had papular lesions on the thighs and pubic area &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Both patients were under immunosuppressive therapy with tacrolimus and mycophenolate mofetil&#44; and trimethoprim&#47;sulfamethoxazole and prednisolone&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In both cases&#44; onychomycosis of the toenails was present&#46; In each case&#44; skin biopsies were performed for routine histology and mycological examination&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Both biopsies showed multiple suppurative granulomas&#44; consisting of numerous neutrophils surrounded by histiocytes and giant cells&#46; Fungal septate hyphae were positive with Periodic AcidSchiff &#40;PAS&#41; and Grocott&#8217;s methenamine silver staining &#40;GMS&#41; &#40;<a class="elsevierStyleCrossRefs" href="#fig0015">Fig&#46; 3 and 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">In both patients&#44; culture for mycology examination was performed on Sabouraud&#8217;s Dextrose Agar &#40;SDA&#41; and <span class="elsevierStyleItalic">Trichophyton rubrum &#40;T&#46; rubrum&#41;</span> was isolated &#40;<a class="elsevierStyleCrossRefs" href="#fig0025">Fig&#46; 5 and 6</a>&#41;&#46; Identification was confirmed by sequencing of ribosomal DNA &#40;GenBank accession number MK967277&#41; and scraping from toenails also isolated <span class="elsevierStyleItalic">T&#46; rubrum</span>&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><elsevierMultimedia ident="fig0030"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Assuming a diagnosis of deep dermatophytosis to <span class="elsevierStyleItalic">T&#46; rubrum</span>&#44; itraconazole 200&#8239;mg daily was initiated&#46; For the next two months&#44; there was difficulty in maintaining tacrolimus levels because of pharmacological interaction with itraconazole&#46; Hence&#44; itraconazole was stopped and terbinafine 250&#8239;mg&#47;day initiated&#44; resulting in clinical improvement&#44; four months after therapy switch&#44; with consequent healing of all lesions and no recurrence after treatment interruption&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Dermatophytosis are fungal infections typically confined to keratinized tissues&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The most frequent causal dermatophyte worldwide is <span class="elsevierStyleItalic">T&#46; rubrum&#46;</span><a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">In immunocompromised patients&#44; dermatophytosis can be more invasive&#44; affecting the dermis and subcutaneous tissues&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Invasive dermatophytosis can be classified as Majocchi&#8217;s granuloma&#44; deep dermatophytosis and disseminated dermatophytosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;4</span></a> The distinction between Majocchi&#8217;s granuloma and deep dermatophytosis is that the latter is not restricted to perifollicular areas&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;4</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">There are less than 100 cases of deep dermatophytosis reported in the literature&#44; mainly occurring in solid organ transplant recipients&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;4&#44;5</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Clinically&#44; deep dermatophytosis manifests usually as multiple papules&#44; plaques&#44; and nodules&#44; most frequently located on the lower extremities&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#8211;7</span></a> Diagnosis should be considered in immunosuppressed patients&#44; particularly when there are associated superficial dermatophytosis&#44; such as onychomycosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a> In the present cases&#44; both patients had concomitant onychomycosis of the toenails caused by <span class="elsevierStyleItalic">T&#46; rubrum</span>&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Confirmation of the infection requires visualization of hyphae in the dermis and identification of the microorganisms in culture or by DNA sequencing&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">There is no consensus on the best treatment&#44; but systemic antifungal therapy with terbinafine or itraconazole is usually effective&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;9</span></a> Rouzaud et al&#46; proposed terbinafine as first-line therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Given the pharmacological interactions between itraconazole and other immunosuppressive medication&#44; we would also advocate for terbinafine as first-line therapy for deep dermatophytosis&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Financial support</span><p id="par0080" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Authors&#8217; contributions</span><p id="par0085" class="elsevierStylePara elsevierViewall">Leandro Silva&#58; Study concept and design&#59; data collection&#44; or analysis and interpretation of data&#59; writing of the manuscript or critical review of important intellectual content&#59; Data collection&#44; analysis and interpretation&#59; Intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied cases&#59; Critical review of the literature&#59; Final approval of the final version of the manuscript&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Jo&#227;o Sousa&#58; Data collection&#44; analysis and interpretation&#59; Intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied cases&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Cristina Toscano&#58; Data collection&#44; analysis and interpretation&#59; Intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied cases&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Isabel Viana&#58; Writing of the manuscript or critical review of important intellectual content&#59; Final approval of the final version of the manuscript&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conflicts of interest</span><p id="par0105" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">In immunosuppressed patients&#44; dermatophytosis can be more invasive&#44; affecting the dermis and subcutaneous tissues&#46; The authors describe the cases of two patients with kidney and heart transplanted&#44; respectively&#44; that developed a deep dermatophytosis caused by <span class="elsevierStyleItalic">Trichophyton rubrum</span>&#44; confirmed by culture and DNA sequencing&#46; Both patients had concomitant onychomycosis&#44; and both were treated with itraconazole for about two months&#44; which was interrupted due to pharmacological interactions with the immunosuppressive drugs and switched to terbinafine&#44; leading to clinical resolution within four months&#46; Deep dermatophytosis should be considered when dealing with immunocompromised patients&#44; especially when a superficial dermatophytosis is present&#46; Oral treatment is necessary and terbinafine is a preferable option in solid organ transplant recipients because it has less pharmacological interactions&#46;</p></span>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41;&#44; First patient &#8211; Erythematous scaly plaque on the right leg&#46; &#40;B&#41;&#44; Second patient &#8211; Violaceous granulomatous nodule surrounded by small erythematous papules on the left thigh&#46;</p>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41;&#44; First patient &#8211; Violaceous papular lesions on the dorsum of the left foot and left toes&#46; &#40;B&#41;&#44; Second patient &#8211; Erythematous grouped papules on the superior portion of the left thigh&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41;&#44; Histopathology of the surgical specimen of the first patient shows diffuse oedema and mixed inflammatory cells with formation of micro abscesses the hyaline&#44; hyphae in multinucleated giant cells with surrounding neutrophils &#40;Hematoxylin &#38; eosin&#44; &#215;100&#41;&#46; &#40;B&#41;&#44; Positive Grocott&#8217;s methenamine silver stain with multiple branching septate hyphae &#40;&#215;400&#41;&#46;</p>"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41;&#44; Histopathology of the surgical specimen of the second patient demonstrating pseudoepitheliomatous hyperplasia&#44; exocytosis of neutrophils and lymphocytes&#44; diffuse oedema mixed inflammatory cells with formation of micro abscesses in the dermis and dermal capillary proliferations&#44; with fungal hyphae &#40;basophilic globular structures&#41; in the multinucleated giant cells &#40;Hematoxylin &#38; eosin&#44; &#215;100&#41;&#46; &#40;B&#41;&#44; Grocott&#8217;s methenamine silver stain branching septate hyphae and multiple round yeast-like structures with pseudobudding &#40;&#215;400&#41;&#46;</p>"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Sabouraud&#8217;s Dextrose Agar culture of the first patient&#46; &#40;A&#41;&#44; Reverse of colony with a yellow-red color&#46; &#40;B&#41;&#44; Front view with white powdery colonies&#46; These aspects are suggestive of <span class="elsevierStyleItalic">T&#46; rubrum&#46;</span></p>"
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      "titulo" => "References"
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Tropical/Infectoparasitary Dermatology
Deep dermatophytosis caused by Trichophyton rubrum in immunocompromised patients
Leandro Silvaa,
Corresponding author
lfssilva@chlo.min-saude.pt

Corresponding author.
, João Sousaa, Cristina Toscanob, Isabel Vianaa
a Department of Dermatology, Hospital Egas Moniz, Centro Hospitalar Lisboa Ocidental, Lisboa, Portugal
b Microbiology Laboratory, Hospital Egas Moniz, Centro Hospitalar Lisboa Ocidental, Lisboa, Portugal
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1</a>&#41;&#46; At the time of consultation&#44; this lesion had two months of evolution and since then&#44; more nodular lesions have appeared on both limbs&#46; She also had papular lesions on the thighs and pubic area &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Both patients were under immunosuppressive therapy with tacrolimus and mycophenolate mofetil&#44; and trimethoprim&#47;sulfamethoxazole and prednisolone&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In both cases&#44; onychomycosis of the toenails was present&#46; In each case&#44; skin biopsies were performed for routine histology and mycological examination&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Both biopsies showed multiple suppurative granulomas&#44; consisting of numerous neutrophils surrounded by histiocytes and giant cells&#46; Fungal septate hyphae were positive with Periodic AcidSchiff &#40;PAS&#41; and Grocott&#8217;s methenamine silver staining &#40;GMS&#41; &#40;<a class="elsevierStyleCrossRefs" href="#fig0015">Fig&#46; 3 and 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">In both patients&#44; culture for mycology examination was performed on Sabouraud&#8217;s Dextrose Agar &#40;SDA&#41; and <span class="elsevierStyleItalic">Trichophyton rubrum &#40;T&#46; rubrum&#41;</span> was isolated &#40;<a class="elsevierStyleCrossRefs" href="#fig0025">Fig&#46; 5 and 6</a>&#41;&#46; Identification was confirmed by sequencing of ribosomal DNA &#40;GenBank accession number MK967277&#41; and scraping from toenails also isolated <span class="elsevierStyleItalic">T&#46; rubrum</span>&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><elsevierMultimedia ident="fig0030"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Assuming a diagnosis of deep dermatophytosis to <span class="elsevierStyleItalic">T&#46; rubrum</span>&#44; itraconazole 200&#8239;mg daily was initiated&#46; For the next two months&#44; there was difficulty in maintaining tacrolimus levels because of pharmacological interaction with itraconazole&#46; Hence&#44; itraconazole was stopped and terbinafine 250&#8239;mg&#47;day initiated&#44; resulting in clinical improvement&#44; four months after therapy switch&#44; with consequent healing of all lesions and no recurrence after treatment interruption&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Dermatophytosis are fungal infections typically confined to keratinized tissues&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The most frequent causal dermatophyte worldwide is <span class="elsevierStyleItalic">T&#46; rubrum&#46;</span><a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">In immunocompromised patients&#44; dermatophytosis can be more invasive&#44; affecting the dermis and subcutaneous tissues&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Invasive dermatophytosis can be classified as Majocchi&#8217;s granuloma&#44; deep dermatophytosis and disseminated dermatophytosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;4</span></a> The distinction between Majocchi&#8217;s granuloma and deep dermatophytosis is that the latter is not restricted to perifollicular areas&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;4</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">There are less than 100 cases of deep dermatophytosis reported in the literature&#44; mainly occurring in solid organ transplant recipients&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;4&#44;5</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Clinically&#44; deep dermatophytosis manifests usually as multiple papules&#44; plaques&#44; and nodules&#44; most frequently located on the lower extremities&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#8211;7</span></a> Diagnosis should be considered in immunosuppressed patients&#44; particularly when there are associated superficial dermatophytosis&#44; such as onychomycosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a> In the present cases&#44; both patients had concomitant onychomycosis of the toenails caused by <span class="elsevierStyleItalic">T&#46; rubrum</span>&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Confirmation of the infection requires visualization of hyphae in the dermis and identification of the microorganisms in culture or by DNA sequencing&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">There is no consensus on the best treatment&#44; but systemic antifungal therapy with terbinafine or itraconazole is usually effective&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;9</span></a> Rouzaud et al&#46; proposed terbinafine as first-line therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Given the pharmacological interactions between itraconazole and other immunosuppressive medication&#44; we would also advocate for terbinafine as first-line therapy for deep dermatophytosis&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Financial support</span><p id="par0080" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Authors&#8217; contributions</span><p id="par0085" class="elsevierStylePara elsevierViewall">Leandro Silva&#58; Study concept and design&#59; data collection&#44; or analysis and interpretation of data&#59; writing of the manuscript or critical review of important intellectual content&#59; Data collection&#44; analysis and interpretation&#59; Intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied cases&#59; Critical review of the literature&#59; Final approval of the final version of the manuscript&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Jo&#227;o Sousa&#58; Data collection&#44; analysis and interpretation&#59; Intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied cases&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Cristina Toscano&#58; Data collection&#44; analysis and interpretation&#59; Intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied cases&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Isabel Viana&#58; Writing of the manuscript or critical review of important intellectual content&#59; Final approval of the final version of the manuscript&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conflicts of interest</span><p id="par0105" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
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            0 => "Dermatofitose"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">In immunosuppressed patients&#44; dermatophytosis can be more invasive&#44; affecting the dermis and subcutaneous tissues&#46; The authors describe the cases of two patients with kidney and heart transplanted&#44; respectively&#44; that developed a deep dermatophytosis caused by <span class="elsevierStyleItalic">Trichophyton rubrum</span>&#44; confirmed by culture and DNA sequencing&#46; Both patients had concomitant onychomycosis&#44; and both were treated with itraconazole for about two months&#44; which was interrupted due to pharmacological interactions with the immunosuppressive drugs and switched to terbinafine&#44; leading to clinical resolution within four months&#46; Deep dermatophytosis should be considered when dealing with immunocompromised patients&#44; especially when a superficial dermatophytosis is present&#46; Oral treatment is necessary and terbinafine is a preferable option in solid organ transplant recipients because it has less pharmacological interactions&#46;</p></span>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41;&#44; First patient &#8211; Erythematous scaly plaque on the right leg&#46; &#40;B&#41;&#44; Second patient &#8211; Violaceous granulomatous nodule surrounded by small erythematous papules on the left thigh&#46;</p>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41;&#44; First patient &#8211; Violaceous papular lesions on the dorsum of the left foot and left toes&#46; &#40;B&#41;&#44; Second patient &#8211; Erythematous grouped papules on the superior portion of the left thigh&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41;&#44; Histopathology of the surgical specimen of the first patient shows diffuse oedema and mixed inflammatory cells with formation of micro abscesses the hyaline&#44; hyphae in multinucleated giant cells with surrounding neutrophils &#40;Hematoxylin &#38; eosin&#44; &#215;100&#41;&#46; &#40;B&#41;&#44; Positive Grocott&#8217;s methenamine silver stain with multiple branching septate hyphae &#40;&#215;400&#41;&#46;</p>"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41;&#44; Histopathology of the surgical specimen of the second patient demonstrating pseudoepitheliomatous hyperplasia&#44; exocytosis of neutrophils and lymphocytes&#44; diffuse oedema mixed inflammatory cells with formation of micro abscesses in the dermis and dermal capillary proliferations&#44; with fungal hyphae &#40;basophilic globular structures&#41; in the multinucleated giant cells &#40;Hematoxylin &#38; eosin&#44; &#215;100&#41;&#46; &#40;B&#41;&#44; Grocott&#8217;s methenamine silver stain branching septate hyphae and multiple round yeast-like structures with pseudobudding &#40;&#215;400&#41;&#46;</p>"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Sabouraud&#8217;s Dextrose Agar culture of the first patient&#46; &#40;A&#41;&#44; Reverse of colony with a yellow-red color&#46; &#40;B&#41;&#44; Front view with white powdery colonies&#46; These aspects are suggestive of <span class="elsevierStyleItalic">T&#46; rubrum&#46;</span></p>"
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Second patient Sabouraud&#8217;s Dextrose Agar culture&#46; &#40;A&#41;&#44; Reverse of colony with a yellow-brown color&#46; &#40;B&#41;&#44; Front view with white powdery colonies&#46; These findings are compatible with <span class="elsevierStyleItalic">T&#46; rubrum&#46;</span></p>"
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      "titulo" => "References"
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Article information
ISSN: 03650596
Original language: English
DOI:10.1016/j.abd.2021.05.014
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Prêmio Bernardo Gontijo
Bernardo Gontijo Award
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Anais Brasileiros de Dermatologia
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