<!DOCTYPE article PUBLIC "-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" "journalpublishing.dtd">
<article article-type="case-report" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML">
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Our Dermatol Online</journal-id>
<journal-title>Our Dermatol Online</journal-title>
<issn pub-type="epub">2081-9390</issn>
<publisher>
<publisher-name>Our Dermatology Online</publisher-name>
<publisher-loc>Poland</publisher-loc>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">OURD-10-267</article-id>
<article-id pub-id-type="doi">10.7241/ourd.20193.10</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Case Report</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Onychomycosis due to mixed infection with non-dermatophyte molds and yeasts</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Tamer</surname>
<given-names>Funda</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="corresp" rid="cor1"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Yuksel</surname>
<given-names>Mehmet Eren</given-names>
</name>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
</contrib-group>
<aff id="aff1"><label>1</label><italic>Ufuk University School of Medicine, Department of Dermatology, Ankara, Turkey</italic></aff>
<aff id="aff2"><label>2</label><italic>Aksaray University School of Medicine, Department of General Surgery, Aksaray, Turkey</italic></aff>
<author-notes>
<corresp id="cor1">
<bold>Corresponding author:</bold> Dr. Funda Tamer, E-mail: <email xlink:href="fundatmr@yahoo.com">fundatmr@yahoo.com</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub">
<year>2019</year>
</pub-date>
<volume>10</volume>
<issue>3</issue>
<fpage>269</fpage>
<lpage>267</lpage>
<history>
<date date-type="received"><day>31</day><month>10</month><year>2018</year></date>
<date date-type="accepted"><day>06</day><month>01</month><year>2019</year></date>
</history>
<permissions>
<copyright-statement>Copyright: &#x000a9; Our Dermatol Online 3</copyright-statement>
<copyright-year>2019</copyright-year>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc-sa/3.0">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p>
</license>
</permissions>
<abstract>
<p>Onychomycosis is the fungal infection of nails which affects 5.5&#x0025; of the general population. Etiologic agents include dermatophytes, non-dermatophyte molds, and yeasts. The infection usually occurs due to dermatophytes. However, non-dermatophyte molds and yeasts have an increasing role in the development of onychomycosis. Detecting causative agent is crucial for the appropriate therapy, as non-dermatophytic molds and yeasts are usually resistant to classical antifungal agents which are used in the treatment of onychomycosis. Hereby, we report a 39-year-old Caucasian male patient with onychomycosis of the great toenails caused by <italic>Aspergillus niger complex, Chaetomium globosum</italic>, <italic>Cladosporium</italic> species, <italic>Candida</italic> species, and onychomycosis of the left thumbnail due to <italic>Aspergillus niger, Chaetomium globosum</italic>, <italic>Cladosporium</italic> species and <italic>Candida lambica</italic>.</p>
</abstract>
<kwd-group>
<kwd>Nail fungus</kwd>
<kwd>Non-dermatophyte molds</kwd>
<kwd>Onychomycosis</kwd>
<kwd>Yeasts</kwd>
</kwd-group>
</article-meta>
</front>
<body>
<sec id="sec1-1" sec-type="introduction">
<title>INTRODUCTION</title>
<p>Onychomycosis is the fungal infection of nails caused by dermatophytes, non-dermatophyte molds, and yeasts. Onychomycosis is the most common nail disease with the prevalence of 5.5&#x0025; all over the world <italic>[<xref ref-type="bibr" rid="ref1">1</xref>]</italic>. It usually affects toenails of adults <italic>[<xref ref-type="bibr" rid="ref2">2</xref>]</italic>. Onychomycosis can lead to pain, paresthesia, difficulties in daily activities, impaired social interactions, and low self-esteem <italic>[<xref ref-type="bibr" rid="ref1">1</xref>,<xref ref-type="bibr" rid="ref3">3</xref>]</italic>. Trauma, tinea pedis, advanced age, diabetes, psoriasis, malignancy and immunosuppression are regarded as risk factors in the etiology of onychomycosis <italic>[<xref ref-type="bibr" rid="ref1">1</xref>]</italic>.</p>
<p>Dermatophytes, especially <italic>T. rubrum</italic> and <italic>T. mentagrophytes</italic> are regarded as the most common causative agents in onychomycosis. Non-dermatophyte molds including <italic>Scopulariopsis brevicaulis, Aspergillus</italic> <italic>spp</italic>, <italic>Acremonium, Fusarium</italic> <italic>spp</italic>, <italic>Alternaria alternate</italic>, and <italic>Neoscytalidium</italic> are detected in approximately 20&#x0025; of the patients. Yeasts (<italic>Candida</italic> <italic>spp</italic>.) are responsible for 10&#x0025;-20&#x0025; of cases with onychomycosis <italic>[<xref ref-type="bibr" rid="ref1">1</xref>]</italic>. Mixed infections with dermatophytes and non-dermatophyte molds in onychomycosis have been rarely reported <italic>[<xref ref-type="bibr" rid="ref4">4</xref>]</italic>.</p>
<p>However, an increasing role of non-dermatophyte molds and yeasts in onychomycosis has been described <italic>[<xref ref-type="bibr" rid="ref5">5</xref>,<xref ref-type="bibr" rid="ref6">6</xref>]</italic>. Furthermore, it has been suggested that non-dermatophytic molds and yeasts are significantly more prevalent causative agents in onychomycosis than dermatophytes <italic>[<xref ref-type="bibr" rid="ref6">6</xref>]</italic>. Ovcina-Kurtovic reported <italic>Candida albicans</italic> as the most common fungus isolated from psoriatic patients with nail involvement <italic>[<xref ref-type="bibr" rid="ref7">7</xref>]</italic>.</p>
<p>Antifungal drug resistance is becoming a healthcare problem as a result of their wide use and availability <italic>[<xref ref-type="bibr" rid="ref8">8</xref>]</italic>. Patients with onychomycosis due to non-dermatophytic molds or yeasts may not respond to systemic antifungals like itraconazole, fluconazole and griseofulvin which are frequently recommended in the treatment of onychomycosis <italic>[<xref ref-type="bibr" rid="ref5">5</xref>]</italic>. Identification of the causative agent with mycological examination is needed for the appropriate treatment and good clinical outcome <italic>[<xref ref-type="bibr" rid="ref6">6</xref>]</italic>.</p>
</sec>
<sec id="sec1-2" sec-type="cases">
<title>CASE REPORT</title>
<p>A 39-year-old Caucasian male patient presented with a 5-year history of discoloration and thickening of the toenails. The patient stated that the symptoms started as a yellow discoloration and thickening under the tip of the right great toenail. Then it spread to the rest of his toenails and left thumbnail gradually. The patient had pain and tenderness in the great toenails while wearing shoes. He did not receive any medication previously. The past medical history was remarkable for chronic peripheral venous insufficiency. He has been wearing compression stockings for the last two years. The family history was unremarkable. The patient denied nail injury, getting pedicure at a nail salon, walking barefoot in public areas like swimming pool, sauna or using an immunosuppressive agent.</p>
<p>Physical examination revealed a squamous plaque on the extensor surface of the left thumb; hyperkeratotic, yellow groove in the midline of the left thumbnail extending from proximal nail fold to distal edge; onycholysis, and white, opaque, friable lesions which created a linear plaque on the left thumbnail (<xref ref-type="fig" rid="F1">Fig. 1</xref>). Moreover, subungual hyperkeratosis, yellow discoloration and onycholysis were observed in all toenails (Figs. <xref ref-type="fig" rid="F2">2</xref>-<xref ref-type="fig" rid="F4">4</xref>).</p>
<fig id="F1">
<label>Figure 1</label>
<caption>
<p>Onycholysis, white, friable lesions, and hyperkeratotic, yellow groove of the left thumbnail. <italic>Aspergillus niger, Chaetomium globosum, Cladosporium</italic> <italic>sp</italic>. and <italic>Candida lambica</italic> were detected from the specimens obtained from the left thumbnail.</p>
</caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="OURD-10-267-g001.tif"/>
</fig>
<fig id="F2">
<label>Figure 2</label>
<caption>
<p>Subungual hyperkeratosis, yellow discoloration and onycholysis of the toenails.</p>
</caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="OURD-10-267-g002.tif"/>
</fig>
<fig id="F3">
<label>Figure 3</label>
<caption>
<p>Total dystrophic onychomycosis of the toenails.</p>
</caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="OURD-10-267-g003.tif"/>
</fig>
<fig id="F4">
<label>Figure 4</label>
<caption>
<p>Closer view of the great toenails. <italic>Aspergillus niger complex, Chaetomium globosum, Cladosporium</italic> species and <italic>Candida</italic> species were identified from the scrapings of great toenails.</p>
</caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="OURD-10-267-g004.tif"/>
</fig>
<p>The laboratory tests including complete blood count, fasting blood glucose, creatinine, total cholesterol, triglyceride, alanine aminotransferase, aspartate aminotransferase, ferritin, folate, vitamin B12, 25-hydroxyvitamin D, zinc and thyroid stimulating hormone levels were all within normal limits.</p>
<p>Mycological examination was performed using conventional methods and matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). The specimens were obtained from scrapings of left thumbnail and from both great toenails. <italic>Aspergillus niger complex, Chaetomium globosum, Cladosporium</italic> species and <italic>Candida</italic> species were identified from the scrapings of bilateral great toenails. <italic>Aspergillus niger, Chaetomium globosum, Cladosporium</italic> <italic>sp</italic>. and <italic>Candida lambica</italic> were detected from the specimens obtained from the left thumbnail. Thus, the diagnosis of onychomycosis due to mixed infection with non-dermatophyte molds and yeasts was made based on clinical findings and MALDI-TOF MS technique.</p>
<p>The patient was advised to get a skin biopsy from the squamous plaque on the left thumb to rule out psoriasis. However, the patient refused the biopsy. He claimed that the lesion occured as a result of repetitive picking of the skin due to psychological stress.</p>
</sec>
<sec id="sec1-3" sec-type="discussion">
<title>DISCUSSION</title>
<p>Onychomycosis can clinically present with subungual hyperkeratosis, onycholysis, melanonychia, and brown, yellow, orange or white discoloration of the nail plate and friable nails. Onychomycosis due to non-dermatophytes has been associated with a marked periungual inflammation <italic>[<xref ref-type="bibr" rid="ref9">9</xref>]</italic>. The non-dermatophyte molds including <italic>Scopulariopsis brevicaulis, Aspergillus</italic> <italic>spp</italic>., <italic>Fusarium</italic> <italic>spp</italic>., <italic>Acremonium</italic> <italic>spp</italic>., <italic>Alternaria</italic> <italic>spp</italic>. and <italic>Neoscytalidium</italic> <italic>spp</italic>. may be the primary pathogens in the development of onychomycosis. Moreover, they may play role as contaminant agents and secondary pathogens. Yeasts like <italic>Candida albicans</italic> and <italic>Candida parapsilosis</italic> cause nail infections only in patients with predisposing factors such as immunosuppression and diabetes <italic>[<xref ref-type="bibr" rid="ref9">9</xref>]</italic>.</p>
<p>Clinical diagnosis should be confirmed with a mycological investigation, since the treatment plan depends on the species of fungi and number of affected nails <italic>[<xref ref-type="bibr" rid="ref9">9</xref>]</italic>. Treatment of patients with nail infections caused by non-dermatophyte organisms like <italic>Fusarium</italic> is usually difficult <italic>[<xref ref-type="bibr" rid="ref10">10</xref>]</italic>.</p>
<p>Treatment options include systemic and topical antifungal agents, chemical or surgical removal of the infected nail, and laser therapy. Oral antifungals may have side effects such as liver damage, and they may cause unwanted drug interactions especially in elderly. Recurrence rate of fungal nail infection is high especially in immunocompromised patients. In addition, diabetes and genetic predisposition to onychomycosis increase the rate of recurrence <italic>[<xref ref-type="bibr" rid="ref10">10</xref>]</italic>.</p>
<p>Hereby, we report a patient with onychomycosis of the left thumbnail and toenails due to mixed infection of non-dermatophyte molds and yeasts including <italic>Chaetomium globosum, Cladosporium</italic> species which are rare in onychomycosis etiology. Detecting the causative agent is crucial for the appropriate therapy, as non-dermatophytic molds and yeasts are usually resistant to classical antifungal agents.</p>
<sec id="sec2-1">
<title>Consent</title>
<p>The examination of the patient was conducted according to the Declaration of Helsinki principles.</p>
</sec>
</sec>
</body>
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<fn-group>
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<p><bold>Source of Support:</bold> Nil</p>
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<fn fn-type="conflict">
<p><bold>Conflict of Interest:</bold> None declared.</p>
</fn>
</fn-group>
</back>
</article>
