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<article xmlns:xlink="http://www.w3.org/1999/xlink" article-type="letter" dtd-version="2.0">
  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">JDERM</journal-id>
      <journal-id journal-id-type="nlm-ta">JMIR Dermatol</journal-id>
      <journal-title>JMIR Dermatology</journal-title>
      <issn pub-type="epub">2562-0959</issn>
      <publisher>
        <publisher-name>JMIR Publications</publisher-name>
        <publisher-loc>Toronto, Canada</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">v6i1e47107</article-id>
      <article-id pub-id-type="pmid">37796583</article-id>
      <article-id pub-id-type="doi">10.2196/47107</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Research Letter</subject>
        </subj-group>
        <subj-group subj-group-type="article-type">
          <subject>Research Letter</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Topical Application of Tea Tree Oil for the Treatment of Verruca Vulgaris</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <name>
            <surname>Dellavalle</surname>
            <given-names>Robert</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib contrib-type="reviewer">
          <name>
            <surname>A. V.</surname>
            <given-names>Dr. Siva Kumar, Ph.D</given-names>
          </name>
        </contrib>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Gasmi </surname>
            <given-names>Maha </given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib id="contrib1" contrib-type="author">
          <name name-style="western">
            <surname>Boopalan</surname>
            <given-names>Deenadayalan</given-names>
          </name>
          <degrees>MD</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0001-9688-1356</ext-link>
        </contrib>
        <contrib id="contrib2" contrib-type="author">
          <name name-style="western">
            <surname>Vijayakumar</surname>
            <given-names>Venugopal</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff2" ref-type="aff">2</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-7422-1856</ext-link>
        </contrib>
        <contrib id="contrib3" contrib-type="author">
          <name name-style="western">
            <surname>Ravi</surname>
            <given-names>Poornima</given-names>
          </name>
          <degrees>BNYS</degrees>
          <xref rid="aff3" ref-type="aff">3</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0001-7220-4676</ext-link>
        </contrib>
        <contrib id="contrib4" contrib-type="author" corresp="yes" equal-contrib="yes">
          <name name-style="western">
            <surname>Kuppusamy</surname>
            <given-names>Maheshkumar</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff4" ref-type="aff">4</xref>
          <address>
            <institution>Department of Physiology</institution>
            <institution>Government Yoga and Naturopathy Medical College and Hospital</institution>
            <addr-line>Anna Arch, Arumbakkam</addr-line>
            <addr-line>Chennai, 600106</addr-line>
            <country>India</country>
            <phone>91 9884591739</phone>
            <email>doctor.mahesh1985@gmail.com</email>
          </address>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-5377-7847</ext-link>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution>Department of Neurology</institution>
        <institution>National Institute of Mental Health and Neurosciences</institution>
        <addr-line>Bengaluru</addr-line>
        <country>India</country>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution>Department of Yoga</institution>
        <institution>Government Yoga and Naturopathy Medical College and Hospital</institution>
        <addr-line>Chennai</addr-line>
        <country>India</country>
      </aff>
      <aff id="aff3">
        <label>3</label>
        <institution>Department of Clinical Research</institution>
        <institution>Sri Ramachandra Institute of Higher Education and Research</institution>
        <addr-line>Chennai</addr-line>
        <country>India</country>
      </aff>
      <aff id="aff4">
        <label>4</label>
        <institution>Department of Physiology</institution>
        <institution>Government Yoga and Naturopathy Medical College and Hospital</institution>
        <addr-line>Chennai</addr-line>
        <country>India</country>
      </aff>
      <author-notes>
        <corresp>Corresponding Author: Maheshkumar Kuppusamy <email>doctor.mahesh1985@gmail.com</email></corresp>
      </author-notes>
      <pub-date pub-type="collection">
        <year>2023</year>
      </pub-date>
      <pub-date pub-type="epub">
        <day>5</day>
        <month>10</month>
        <year>2023</year>
      </pub-date>
      <volume>6</volume>
      <elocation-id>e47107</elocation-id>
      <history>
        <date date-type="received">
          <day>8</day>
          <month>3</month>
          <year>2023</year>
        </date>
        <date date-type="rev-request">
          <day>28</day>
          <month>8</month>
          <year>2023</year>
        </date>
        <date date-type="rev-recd">
          <day>6</day>
          <month>9</month>
          <year>2023</year>
        </date>
        <date date-type="accepted">
          <day>25</day>
          <month>9</month>
          <year>2023</year>
        </date>
      </history>
      <copyright-statement>©Deenadayalan Boopalan, Venugopal Vijayakumar, Poornima Ravi, Maheshkumar Kuppusamy. Originally published in JMIR Dermatology (http://derma.jmir.org), 05.10.2023.</copyright-statement>
      <copyright-year>2023</copyright-year>
      <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/">
        <p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Dermatology, is properly cited. The complete bibliographic information, a link to the original publication on http://derma.jmir.org, as well as this copyright and license information must be included.</p>
      </license>
      <self-uri xlink:href="https://derma.jmir.org/2023/1/e47107" xlink:type="simple"/>
      <kwd-group>
        <kwd>aromatherapy</kwd>
        <kwd>human papillomavirus</kwd>
        <kwd>naturopathy</kwd>
        <kwd>tea tree oil</kwd>
        <kwd>warts</kwd>
        <kwd>verruca vulgaris</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="introduction">
      <title>Introduction</title>
      <p>Warts (verruca vulgaris) are benign epithelial proliferations associated with human papillomavirus (HPV) infection. They are a DNA virus belonging to the Papillomaviridae family [<xref ref-type="bibr" rid="ref1">1</xref>]. Worldwide, 10% of the population is affected, and the prevalence is high in children attending school [<xref ref-type="bibr" rid="ref2">2</xref>]. Common warts are excessive growths with an irregular surface ranging from 1 millimeter to several centimeters and are commonly seen on the upper and lower extremities [<xref ref-type="bibr" rid="ref2">2</xref>]. Conventional treatment for warts includes topical application of salicylic acid, podophyllotoxin, trichloroacetic acid, formaldehyde, 5-fluorouracil, and photodynamic therapy [<xref ref-type="bibr" rid="ref1">1</xref>]. Procedures such as cryotherapy, laser ablation, electrocautery, and surgical excision are painful and have higher chances of reoccurrence [<xref ref-type="bibr" rid="ref1">1</xref>]. In aromatherapy, tea tree oil (TTO), extracted through steam distillation of the leaves and terminal branches of the Australian plant <italic>Melaleuca alternifolia</italic>, is used for the management of various dermatological conditions, including HPV [<xref ref-type="bibr" rid="ref3">3</xref>,<xref ref-type="bibr" rid="ref4">4</xref>], by naturopathy physicians. This letter aims to present TTO as a potential remedy for HPV warts, highlighting its properties, benefits, and the need for further research to establish its effectiveness and safety.</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <p>We performed a comprehensive literature search to include original articles, case reports and case series, and abstracts that discussed the effect of TTO on HPV verruca vulgaris; in PubMed, Embase, and Google Scholar; and were published on April 9, 2022, or earlier. Reviews and articles that used TTO with other interventions were excluded. The following keywords were used: “tea tree oil” OR “aromatherapy” OR “naturopathy” AND “human papillomavirus” OR “HPV” OR “verruca vulgaris” OR “warts.”</p>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <p>A total of 4 articles involving 5 patients with warts treated with aromatherapy were included (<xref ref-type="table" rid="table1">Table 1</xref>). Warts were predominantly found on the upper and lower extremities, except for one case where the location was periungual [<xref ref-type="bibr" rid="ref5">5</xref>]. The efficacy was assessed by using the visual analog scale [<xref ref-type="bibr" rid="ref3">3</xref>] and clinical photographs daily [<xref ref-type="bibr" rid="ref1">1</xref>,<xref ref-type="bibr" rid="ref3">3</xref>]. Additionally, a follow-up was conducted to monitor for any recurrence [<xref ref-type="bibr" rid="ref1">1</xref>]. All the studies included in this analysis reported complete clearance of warts.</p>
      <table-wrap position="float" id="table1">
        <label>Table 1</label>
        <caption>
          <p>Characteristics of the studies included in the research letter.</p>
        </caption>
        <table width="1000" cellpadding="5" cellspacing="0" border="1" rules="groups" frame="hsides">
          <col width="30"/>
          <col width="220"/>
          <col width="130"/>
          <col width="100"/>
          <col width="120"/>
          <col width="130"/>
          <col width="140"/>
          <col width="130"/>
          <thead>
            <tr valign="top">
              <td colspan="2">Study, year, and participants</td>
              <td>Country</td>
              <td>Age (years)</td>
              <td>Diagnosed by</td>
              <td>Site of warts</td>
              <td>Intervention details</td>
              <td>Outcome</td>
            </tr>
          </thead>
          <tbody>
            <tr valign="top">
              <td colspan="8">
                <bold>Millar and Moore [<xref ref-type="bibr" rid="ref4">4</xref>], 2008</bold>
              </td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>Female pediatric patient</td>
              <td>United Kingdom</td>
              <td>7</td>
              <td>Dermatologist</td>
              <td>Distal phalanges of the right middle finger</td>
              <td>Topical application of tea tree oil once daily for 12 days</td>
              <td>Complete clearance of warts without reoccurrence</td>
            </tr>
            <tr valign="top">
              <td colspan="2">
                <bold>Alsanad and Alkhamees [<xref ref-type="bibr" rid="ref3">3</xref>], 2016</bold>
              </td>
              <td>Saudi Arabia</td>
              <td>
                <break/>
              </td>
              <td>Dermatologist</td>
              <td>
                <break/>
              </td>
              <td>
                <break/>
              </td>
              <td>Complete clearance of warts without reoccurrence</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>Male child</td>
              <td>
                <break/>
              </td>
              <td>9</td>
              <td>
                <break/>
              </td>
              <td>Left sole</td>
              <td>Topical application of tea tree oil twice a day for 20 days</td>
              <td>
                <break/>
              </td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>Male child</td>
              <td>
                <break/>
              </td>
              <td>14</td>
              <td>
                <break/>
              </td>
              <td>Proximal phalanges of the right little finger</td>
              <td>Topical application of tea tree oil twice a day for 10 days</td>
              <td>
                <break/>
              </td>
            </tr>
            <tr valign="top">
              <td colspan="8">
                <bold>Lim et al [<xref ref-type="bibr" rid="ref5">5</xref>], 2020</bold>
              </td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>Female child</td>
              <td>South Korea</td>
              <td>12</td>
              <td>Dermatologist</td>
              <td>Periungual and plantar</td>
              <td>Topical application of tea tree oil for 9 months</td>
              <td>Complete clearance of warts without reoccurrence</td>
            </tr>
            <tr valign="top">
              <td colspan="8">
                <bold>Deenadayalan et al [<xref ref-type="bibr" rid="ref1">1</xref>], 2022</bold>
              </td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>Adult female</td>
              <td>India</td>
              <td>22</td>
              <td>Dermatologist</td>
              <td>Distal phalanges of the right hand</td>
              <td>Topical application of tea tree oil once a day for 7 days, afterward alternative day for 2 weeks</td>
              <td>Complete clearance of warts without reoccurrence</td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>This research letter indicates that TTO can be beneficial in treating warts, which are caused by HPV and commonly occur in pediatric and school-aged children. The potent anti-inflammatory and antiviral properties of TTO have been widely used to treat HPV infections. In vitro studies have also used TTO to treat herpes simplex virus [<xref ref-type="bibr" rid="ref4">4</xref>]. Terpinene-4-ol and α-terpineol in TTO are known for their antiviral property and inhibit viral replication in both enveloped and nonenveloped viruses [<xref ref-type="bibr" rid="ref4">4</xref>]. Terpinene-4-ol can inhibit the synthesis of proinflammatory cytokines, tumor necrosis factor, interleukin-1 (IL-1), IL-8, and prostaglandin E2 while increasing anti-inflammatory cytokines (IL-10 and IL-4), thereby reducing pain [<xref ref-type="bibr" rid="ref1">1</xref>]. In addition to pain management and warts clearance, a pleasant scent may play a role in patient satisfaction. The treatment is also less expensive and has no adverse effects. The limitation of this letter was using single case reports with a small number of patients.</p>
      <p>TTO should be considered a safe, cost-effective, noninvasive modality in the management of HPV warts. More research is necessary to understand the clinical applications and other long-term systemic effects.</p>
    </sec>
  </body>
  <back>
    <app-group/>
    <glossary>
      <title>Abbreviations</title>
      <def-list>
        <def-item>
          <term id="abb1">HPV</term>
          <def>
            <p>human papillomavirus</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb2">IL</term>
          <def>
            <p>interleukin</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb3">TTO</term>
          <def>
            <p>tea tree oil</p>
          </def>
        </def-item>
      </def-list>
    </glossary>
    <fn-group>
      <fn fn-type="conflict">
        <p>None declared.</p>
      </fn>
    </fn-group>
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