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characterized by reduced production of interferon-&#947;&#44; interleukin-17&#44; and interleukin-22 cytokines&#44; crucial for antifungal defense of the skin and mucous membranes&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;4</span></a> To the best of our knowledge&#44; this is the first report in which the detected <span class="elsevierStyleItalic">STAT1</span> variant was documented in association with CMCC&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Typically&#44; this form of the disease manifests as erythematous scaling crusted&#44; hyperkeratotic generalized plaques before the age of five&#44; sometimes accompanied by paronychia&#44; hyperkeratosis and nail dystrophy&#46; The oral mucosa is the most frequently affected&#44; although the esophageal&#44; genital and laryngeal mucosa can be affected as well&#46; In addition to chronic <span class="elsevierStyleItalic">Candida</span> infection&#44; there is also increased susceptibility to dermatophyte and bacterial infections&#44; and up to 50&#37; of the patients have associated hypothyroidism&#44; inflammatory bowel disease&#44; or associated autoimmune cytopenias&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">The analysis of relevant genes&#44; such as <span class="elsevierStyleItalic">STAT1</span>&#44; <span class="elsevierStyleItalic">AIRE</span> and <span class="elsevierStyleItalic">CARD9</span>&#44; is the only definitive laboratory test for the diagnosis of CMCC&#46; Other immunodeficiencies&#44; including SCID&#44; HIES&#44; and AIDS&#44; can result in chronic candidiasis&#44; but almost invariably course with invasive <span class="elsevierStyleItalic">Candida</span> infections and additional clinical-laboratory characteristics&#46; In SCID&#44; severe disturbances in T-&#44; B-&#44; and sometimes natural killer-cell development and function result in failure to thrive&#44; chronic diarrhea&#44; and recurrent severe infections with common viral pathogens &#40;such as respiratory syncytial virus&#44; adenovirus&#44; and cytomegalovirus&#41;&#44; and opportunistic microorganisms &#8211; which&#44; in general&#44; lead to death in the first year of life&#46; HIES&#44; in turn&#44; is characterized by persistent generalized eczema&#44; deep staphylococcal abscesses&#44; <span class="elsevierStyleItalic">Aspergillus</span> infections&#44; dimorphic features and recurrent fractures&#44; in addition to increased levels of IgE&#44; eosinophilia and mutation in the <span class="elsevierStyleItalic">STAT3</span> gene&#46; Finally&#44; AIDS is differentiated from CMCC by positive HIV serology&#44; reduced CD4&#43; T-cell count&#44; and occurrence of opportunistic infections&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Treatment of CMCC involves infection control and management of associated endocrine and autoimmune disorders&#46; <span class="elsevierStyleItalic">Candida</span> infections can be controlled with prolonged use of azole antifungals&#44; preferably fluconazole 100&#8210;200&#8239;mg&#47;day&#46; Other therapies have been described in isolated reports to control the immune disorder&#44; such as thymus and hematopoietic cell transplantation&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Recently&#44; some studies have reported good disease control with the use of JAK inhibitors&#44; including ruxolitinib and baricitinib&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Financial support</span><p id="par0065" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Authors&#39; contributions</span><p id="par0070" class="elsevierStylePara elsevierViewall">Nathalia Chebli de Abreu&#58; Design and planning of the study&#59; collection&#44; analysis&#44; and interpretation of data&#59; critical review of the literature&#59; drafting and editing of the manuscript&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Samuel Duarte Timponi France&#58; Critical review of the literature&#59; drafting and editing of the manuscript&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Hyllo Baeta Marcelo J&#250;nior&#58; Collection&#44; analysis and interpretation of data&#59; critical review of the literature&#59; critical review of the manuscript&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Amanda Neto Ladeira&#58; Design and planning of the study&#59; collection&#44; analysis&#44; and interpretation of data&#59; approval of the final version of the manuscript&#59; intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied case&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conflicts of interest</span><p id="par0090" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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Letter - Clinical
Case for diagnosis. Disseminated erythematous and scaly plaques: chronic mucocutaneous candidiasis
Nathalia Chebli de Abreua,b,
Corresponding author
nathaliachebli@gmail.com

Corresponding author.
, Samuel Duarte Timponi Françaa,b, Hyllo Baeta Marcelo Júniorc, Amanda Neto Ladeiraa
a Department of Dermatology, Hospital Infantil João Paulo II, Fundação Hospitalar do Estado de Minas Gerais, Belo Horizonte, MG, Brazil
b Department of Dermatology, Hospital Eduardo de Menezes, Fundação Hospitalar do Estado de Minas Gerais, Belo Horizonte, MG, Brazil
c Department of Mycology, Fundação Ezequiel Dias, Belo Horizonte, MG, Brazil
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and yeasts &#8211; later identified as <span class="elsevierStyleItalic">Microsporum gypseum</span> and <span class="elsevierStyleItalic">Candida albicans</span> by MALDI-TOF &#40;Matrix-assisted laser desorption ionization time-of-flight&#41; mass spectrometry&#46; Histopathology revealed irregular acanthosis&#44; spongiosis&#44; keratotic crust&#44; and dermal edema&#44; in addition to numerous hyphae and spores restricted to the stratum corneum &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; The genome analysis identified a rare heterozygous mutation in exon 7 of the signal transducer and activator of transcription 1 &#40;<span class="elsevierStyleItalic">STAT1</span>&#41; gene&#59; variant c&#46;501A&#8594;C&#59; p&#46;Gln167His&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">What&#39;s your diagnosis&#63;</span><p id="par0015" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">a&#41;</span><p id="par0020" class="elsevierStylePara elsevierViewall">Acquired Immunodeficiency Syndrome &#40;AIDS&#41;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">b&#41;</span><p id="par0025" class="elsevierStylePara elsevierViewall">Severe Combined Immunodeficiency &#40;SCID&#41;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">c&#41;</span><p id="par0030" class="elsevierStylePara elsevierViewall">Chronic Mucocutaneous Candidiasis &#40;CMCC&#41;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">d&#41;</span><p id="par0035" class="elsevierStylePara elsevierViewall">Hyper-IgE Syndrome &#40;HIES&#41;</p></li></ul></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Discussion</span><p id="par0040" class="elsevierStylePara elsevierViewall">Based on the clinical-laboratory correlation&#44; the diagnosis of chronic mucocutaneous candidiasis &#40;CMCC&#41; was established due to the <span class="elsevierStyleItalic">STAT1</span> gene mutation&#44; in addition to extensive dermatophytosis&#46; Complementary exams&#44; including indirect Coombs&#44; thyroid function&#44; anti-HIV I and II serology&#44; autoantibodies&#44; immunoglobulin measurement and lymphocyte immunophenotyping were normal&#46; Oral fluconazole was started with partial regression of the lesions &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">CMCC is a heterogeneous group of rare syndromes characterized by persistent&#44; non-invasive <span class="elsevierStyleItalic">Candida spp</span> infections of the skin&#44; nails&#44; and mucous membranes caused by primary immunological defects&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleItalic">STAT1</span> gain-of-function mutations underlie the autosomal dominant form of the disease and result in defective Th1 and Th17 cell responses&#44; characterized by reduced production of interferon-&#947;&#44; interleukin-17&#44; and interleukin-22 cytokines&#44; crucial for antifungal defense of the skin and mucous membranes&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;4</span></a> To the best of our knowledge&#44; this is the first report in which the detected <span class="elsevierStyleItalic">STAT1</span> variant was documented in association with CMCC&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Typically&#44; this form of the disease manifests as erythematous scaling crusted&#44; hyperkeratotic generalized plaques before the age of five&#44; sometimes accompanied by paronychia&#44; hyperkeratosis and nail dystrophy&#46; The oral mucosa is the most frequently affected&#44; although the esophageal&#44; genital and laryngeal mucosa can be affected as well&#46; In addition to chronic <span class="elsevierStyleItalic">Candida</span> infection&#44; there is also increased susceptibility to dermatophyte and bacterial infections&#44; and up to 50&#37; of the patients have associated hypothyroidism&#44; inflammatory bowel disease&#44; or associated autoimmune cytopenias&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">The analysis of relevant genes&#44; such as <span class="elsevierStyleItalic">STAT1</span>&#44; <span class="elsevierStyleItalic">AIRE</span> and <span class="elsevierStyleItalic">CARD9</span>&#44; is the only definitive laboratory test for the diagnosis of CMCC&#46; Other immunodeficiencies&#44; including SCID&#44; HIES&#44; and AIDS&#44; can result in chronic candidiasis&#44; but almost invariably course with invasive <span class="elsevierStyleItalic">Candida</span> infections and additional clinical-laboratory characteristics&#46; In SCID&#44; severe disturbances in T-&#44; B-&#44; and sometimes natural killer-cell development and function result in failure to thrive&#44; chronic diarrhea&#44; and recurrent severe infections with common viral pathogens &#40;such as respiratory syncytial virus&#44; adenovirus&#44; and cytomegalovirus&#41;&#44; and opportunistic microorganisms &#8211; which&#44; in general&#44; lead to death in the first year of life&#46; HIES&#44; in turn&#44; is characterized by persistent generalized eczema&#44; deep staphylococcal abscesses&#44; <span class="elsevierStyleItalic">Aspergillus</span> infections&#44; dimorphic features and recurrent fractures&#44; in addition to increased levels of IgE&#44; eosinophilia and mutation in the <span class="elsevierStyleItalic">STAT3</span> gene&#46; Finally&#44; AIDS is differentiated from CMCC by positive HIV serology&#44; reduced CD4&#43; T-cell count&#44; and occurrence of opportunistic infections&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Treatment of CMCC involves infection control and management of associated endocrine and autoimmune disorders&#46; <span class="elsevierStyleItalic">Candida</span> infections can be controlled with prolonged use of azole antifungals&#44; preferably fluconazole 100&#8210;200&#8239;mg&#47;day&#46; Other therapies have been described in isolated reports to control the immune disorder&#44; such as thymus and hematopoietic cell transplantation&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Recently&#44; some studies have reported good disease control with the use of JAK inhibitors&#44; including ruxolitinib and baricitinib&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Financial support</span><p id="par0065" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Authors&#39; contributions</span><p id="par0070" class="elsevierStylePara elsevierViewall">Nathalia Chebli de Abreu&#58; Design and planning of the study&#59; collection&#44; analysis&#44; and interpretation of data&#59; critical review of the literature&#59; drafting and editing of the manuscript&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Samuel Duarte Timponi France&#58; Critical review of the literature&#59; drafting and editing of the manuscript&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Hyllo Baeta Marcelo J&#250;nior&#58; Collection&#44; analysis and interpretation of data&#59; critical review of the literature&#59; critical review of the manuscript&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Amanda Neto Ladeira&#58; Design and planning of the study&#59; collection&#44; analysis&#44; and interpretation of data&#59; approval of the final version of the manuscript&#59; intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied case&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conflicts of interest</span><p id="par0090" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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Article information
ISSN: 03650596
Original language: English
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