<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.2 20190208//EN" "http://jats.nlm.nih.gov/publishing/1.2/JATS-journalpublishing1.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="other" dtd-version="1.2" xml:lang="en">
    <front>
        <journal-meta>
            <journal-id journal-id-type="pmc">F1000Research</journal-id>
            <journal-title-group>
                <journal-title>F1000Research</journal-title>
            </journal-title-group>
            <issn pub-type="epub">2046-1402</issn>
            <publisher>
                <publisher-name>F1000 Research Limited</publisher-name>
                <publisher-loc>London, UK</publisher-loc>
            </publisher>
        </journal-meta>
        <article-meta>
            <article-id pub-id-type="doi">10.12688/f1000research.179446.1</article-id>
            <article-categories>
                <subj-group subj-group-type="heading">
                    <subject>Study Protocol</subject>
                </subj-group>
                <subj-group>
                    <subject>Articles</subject>
                </subj-group>
            </article-categories>
            <title-group>
                <article-title>Illuminating diagnostic pathways: study protocol for a prospective observational study comparing inflammoscopy and ultraviolet-induced fluorescence dermoscopy with histopathology in cutaneous lichen planus.</article-title>
                <fn-group content-type="pub-status">
                    <fn>
                        <p>[version 1; peer review: 1 approved with reservations]</p>
                    </fn>
                </fn-group>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author" corresp="yes">
                    <name>
                        <surname>H</surname>
                        <given-names>Varun</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Project Administration</role>
                    <role content-type="http://credit.niso.org/">Visualization</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0009-0004-1218-0181</uri>
                    <xref ref-type="corresp" rid="c1">a</xref>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Singh</surname>
                        <given-names>Adarshlata</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Project Administration</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Visualization</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Madke</surname>
                        <given-names>Bhushan</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Project Administration</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0000-0003-2704-9165</uri>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>sarda</surname>
                        <given-names>Bhakti</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Resources</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Mittal</surname>
                        <given-names>Anurag</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Software</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Kacchawa</surname>
                        <given-names>Naman</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Visualization</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0009-0006-9981-0549</uri>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Singh</surname>
                        <given-names>Swati</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Resources</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <aff id="a1">
                    <label>1</label>Department of Dermatology,Venereology and Leprosy, Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, 442001, India</aff>
            </contrib-group>
            <author-notes>
                <corresp id="c1">
                    <label>a</label>
                    <email xlink:href="mailto:varunhanumanthaiah@hotmail.com">varunhanumanthaiah@hotmail.com</email>
                </corresp>
                <fn fn-type="conflict">
                    <p>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>17</day>
                <month>4</month>
                <year>2026</year>
            </pub-date>
            <pub-date pub-type="collection">
                <year>2026</year>
            </pub-date>
            <volume>15</volume>
            <elocation-id>551</elocation-id>
            <history>
                <date date-type="accepted">
                    <day>27</day>
                    <month>3</month>
                    <year>2026</year>
                </date>
            </history>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2026 H V et al.</copyright-statement>
                <copyright-year>2026</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <self-uri content-type="pdf" xlink:href="https://f1000research.com/articles/15-551/pdf"/>
            <abstract>
                <sec>
                    <title>Introduction</title>
                    <p>Lichen planus (LP) is an inflammatory dermatosis that is often diagnosed clinically but may require histopathological confirmation in equivocal cases. Dermoscopy enhances the visualisation of subsurface morphologic features and may improve non-invasive diagnosis. Ultraviolet-induced fluorescence dermoscopy (UVFD) is an emerging modality that may reveal additional diagnostic clues through the interaction of ultraviolet light with cutaneous structures. This study aims to investigate the dermoscopic and UVFD features of cutaneous LP, correlate them with histopathological findings, and evaluate the diagnostic accuracy of dermoscopy using histopathology as the reference standard.</p>
                </sec>
                <sec>
                    <title>Methods</title>
                    <p>This is a two-year prospective observational study to be conducted in the Dermatology outpatient department of Acharya Vinoba Bhave Rural Hospital, Wardha, India. Adults with clinically suspected cutaneous LP who are willing to undergo biopsy will be enrolled after written informed consent. Dermoscopic and UVFD findings from selected lesions will be documented before punch biopsy. Histopathological examination will serve as the reference standard. Dermoscopic, UVFD, and histopathological findings will be correlated using imaging alignment methods and image analysis software, including ImageJ and QuPath. Diagnostic accuracy measures, including sensitivity, specificity, positive predictive value, negative predictive value, agreement statistics, and receiver operating characteristic analysis, will be calculated.</p>
                </sec>
                <sec>
                    <title>Ethics and dissemination</title>
                    <p>The study has received approval from the Institutional Ethics Committee of Datta Meghe Institute of Higher Education and Research, Wardha, India (
                        <bold>study approval number: DMIHER (DU)/IEC/2024/141</bold>; IEC registration/re-registration number: 
                        <bold>ECR/440/Inst/MH/2013/RR-2019</bold>). Written informed consent will be obtained from all participants prior to enrolment. The findings will be disseminated through peer-reviewed publication and academic presentation.</p>
                    <p>

                        <underline>

                            <bold>Trial registration:</bold>
</underline> Clinical Trials Registry&#x2013;India (CTRI): CTRI/2025/05/086296; Reference No. REF/2024/03/080873.</p>
                </sec>
            </abstract>
            <kwd-group kwd-group-type="author">
                <kwd>Lichen planus</kwd>
                <kwd>cutaneous lichen planus</kwd>
                <kwd>lichenoid dermatosis</kwd>
                <kwd>dermoscopy</kwd>
                <kwd>inflamoscopy</kwd>
                <kwd>ultraviolet-induced fluorescence dermoscopy</kwd>
                <kwd>UVFD</kwd>
                <kwd>histopathology.</kwd>
            </kwd-group>
            <funding-group>
                <award-group id="fund-1">
                    <funding-source>The author(s) declared that NO grants were involved in supporting this work.</funding-source>
                </award-group>
                <funding-statement>The author(s) declared that no grants were involved in supporting this work.</funding-statement>
            </funding-group>
        </article-meta>
    </front>
    <body>
        <sec id="sec4" sec-type="intro">
            <title>Introduction</title>
            <p>The exact pathogenesis of LP remains uncertain; however, it is postulated that keratinocyte damage occurs through CD8+ cytotoxic T-cell-mediated apoptosis following antigen presentation by basal keratinocytes. A deficiency in TGF-&#x03b2;1-mediated immunosuppression may lead to sustained overactivity of these cytotoxic T cells, contributing to the chronicity of the disease.
                <sup>
                    <xref ref-type="bibr" rid="ref1">1</xref>,
                    <xref ref-type="bibr" rid="ref2">2</xref>
                </sup>
            </p>
            <p>Accurate epidemiologic data on LP are limited. A systematic review and meta-analysis conducted in September 2019 reported a global pooled prevalence of LP at 1.01% with significant geographical variation.
                <sup>
                    <xref ref-type="bibr" rid="ref3">3</xref>
                </sup> Due to the lack of robust, large-scale epidemiologic data specifically on cutaneous LP, we have used published data on oral LP as a proxy for estimating prevalence. We acknowledge this limitation, and an interim analysis is planned to validate the prevalence assumptions within our study population.</p>
            <p>Currently, the diagnosis of lichen planus relies primarily on clinical evaluation, including assessment of the &#x201c;6P&#x2019;s&#x201d; (planar, purple, polygonal, pruritic, papules and plaques) and distribution that commonly affects the skin of the flexor surfaces. The presence of Wickham striae, which are prominent, lacy, reticular white lines, is considered diagnostic. However, differential diagnoses such as Prurigo, Lupus Erythematosus, erythema dyschromicum perstans, psoriasis, secondary syphilis, pityriasis rosea, lichen nitidus, graft versus host disease, and keratosis lichenoides chronica must be ruled out, often necessitating histopathological confirmation via excisional biopsy.
                <sup>
                    <xref ref-type="bibr" rid="ref4">4</xref>,
                    <xref ref-type="bibr" rid="ref5">5</xref>
                </sup>
            </p>
            <p>Dermoscopy enhances the visualisation of subtle skin changes that are not apparent to the naked eye, thereby revolutionising the diagnosis of inflammatory dermatoses. Dermoscopic patterns have been shown to correlate with histopathological features; for example, Wickham striae (WS) reflect focal thickening of the stratum granulosum, while red dots indicate vascular changes.
                <sup>
                    <xref ref-type="bibr" rid="ref6">6</xref>&#x2013;
                    <xref ref-type="bibr" rid="ref9">9</xref>
                </sup>
            </p>
            <p>Histologically, LP is characterised by hyperkeratosis (typically orthokeratosis), acanthosis, and irregular thickening of the stratum granulosum (hypergranulosis) resulting in the &#x201c;saw-tooth&#x201d; appearance of the rete ridges. Basal cell liquefaction leads to the formation of apoptotic keratinocytes (Civatte or cytoid bodies) and the development of a cleft (Max Joseph space). A dense band-like lymphocytic infiltrate (interface dermatitis) is observed at the dermo-epidermal junction, sometimes accompanied by a few plasma cells, and in drug-induced cases, eosinophils.
                <sup>
                    <xref ref-type="bibr" rid="ref4">4</xref>,
                    <xref ref-type="bibr" rid="ref10">10</xref>&#x2013;
                    <xref ref-type="bibr" rid="ref12">12</xref>
                </sup>
            </p>
            <p>Dermoscopy offers an attractive adjunct to reduce the need for invasive biopsies. UVFD, by providing additional optical data (through penetration, absorption, scattering, and Stokes-shift phenomena), may further enhance diagnostic accuracy.
                <sup>
                    <xref ref-type="bibr" rid="ref13">13</xref>&#x2013;
                    <xref ref-type="bibr" rid="ref16">16</xref>
                </sup>
            </p>
            <p>Although some literature suggests that UVFD may be less effective than non-contact polarised dermoscopy in diagnosing LP, we hypothesise that its integration will improve diagnostic accuracy by revealing both specific and non-specific features that correlate with histopathological findings. For instance, loose keratin may appear as white lines and compact keratin plugs as yellow clods on conventional dermoscopy, whereas UVFD may reveal white fluorescence in both, confirming keratin&#x2019;s natural fluorescence. In early-stage disease, when vascular structures are not distinctly visible as red dots or clods, UVFD may delineate them as dark structureless areas at the lesion periphery. Accordingly, an additional rationale for this study is to document both specific and non-specific UVFD features and correlate them with polarised dermoscopy and histopathological findings.
                <sup>
                    <xref ref-type="bibr" rid="ref13">13</xref>,
                    <xref ref-type="bibr" rid="ref17">17</xref>,
                    <xref ref-type="bibr" rid="ref18">18</xref>
                </sup>
            </p>
        </sec>
        <sec id="sec5">
            <title>Protocol</title>
            <sec id="sec6">
                <title>Primary outcome</title>
                <p>

                    <list list-type="order">
                        <list-item>
                            <label>1.</label>
                            <p>To determine the diagnostic accuracy (sensitivity, specificity, positive predictive value, and negative predictive value) of dermoscopy in diagnosing cutaneous lichen planus, using histopathology as the reference standard.</p>
                        </list-item>
                    </list>
                </p>
            </sec>
            <sec id="sec7">
                <title>Secondary outcomes</title>
                <p>

                    <list list-type="order">
                        <list-item>
                            <label>1.</label>
                            <p>To investigate the specific and non-specific dermoscopic features of cutaneous lichen planus.</p>
                        </list-item>
                        <list-item>
                            <label>2.</label>
                            <p>To document the specific and non-specific ultraviolet-induced fluorescence dermoscopic (UVFD) findings in cutaneous lichen planus.</p>
                        </list-item>
                        <list-item>
                            <label>3.</label>
                            <p>To correlate dermoscopic and UVFD findings with histopathology.</p>
                        </list-item>
                        <list-item>
                            <label>4.</label>
                            <p>To assess agreement between dermoscopic impression and histopathological diagnosis.</p>
                        </list-item>
                        <list-item>
                            <label>5.</label>
                            <p>Predictive performance measures, including positive predictive value, negative predictive value, and area under the receiver operating characteristic curve, where applicable.</p>
                        </list-item>
                    </list>
                </p>
            </sec>
            <sec id="sec8">
                <title>Study design and setting</title>
                <p>This is a two-year prospective observational analytical study to be conducted in the Department of Dermatology, Venereology and Leprosy at Acharya Vinoba Bhave Rural Hospital (AVBRH), a tertiary care teaching hospital in Wardha, Maharashtra, India. The overall study workflow is outlined in 
                    <xref ref-type="fig" rid="f1">
Figure 1</xref>. Dermoscopic findings will be recorded using a predefined data collection form (
                    <xref ref-type="fig" rid="f2">
Figure 2</xref>), and histopathological findings will be documented using a predefined histopathology template (
                    <xref ref-type="fig" rid="f3">
Figure 3</xref>).</p>
                <fig fig-type="figure" id="f1" orientation="portrait" position="float">
                    <label>
Figure 1. </label>
                    <caption>
                        <title>Flowchart outlining the planned strategy for participant recruitment, data collection, and analysis.</title>
                    </caption>
                    <graphic id="gr1" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/197960/3b375550-b094-40c9-bca5-5c53c9d22817_figure1.gif"/>
                </fig>
                <fig fig-type="figure" id="f2" orientation="portrait" position="float">
                    <label>
Figure 2. </label>
                    <caption>
                        <title>Data collection form for recording dermoscopic features in suspected cutaneous lichen planus.</title>
                    </caption>
                    <graphic id="gr2" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/197960/3b375550-b094-40c9-bca5-5c53c9d22817_figure2.gif"/>
                </fig>
                <fig fig-type="figure" id="f3" orientation="portrait" position="float">
                    <label>
Figure 3. </label>
                    <caption>
                        <title>Data collection form for documenting histopathological features in suspected cutaneous lichen planus.</title>
                    </caption>
                    <graphic id="gr3" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/197960/3b375550-b094-40c9-bca5-5c53c9d22817_figure3.gif"/>
                </fig>
            </sec>
            <sec id="sec9">
                <title>Operational diagnostic criteria</title>
                <p>For the purposes of this study, the presence of Wickham striae on dermoscopy will be considered highly suggestive of lichen planus. In lesions without obvious Wickham striae, the presence of at least three of the following five dermoscopic domains will be recorded as supportive of a provisional dermoscopic diagnosis: background colour, vascular pattern, pigmentation, surface changes, and other associated features. UVFD findings will be documented descriptively and explored as adjunctive diagnostic features.</p>
                <p>Histopathologically, wedge-shaped hypergranulosis, band-like lymphocytic infiltrate, Max Joseph spaces, and Civatte bodies will be considered major features, while other compatible findings will be treated as minor features. A histopathological diagnosis of lichen planus will require either two major features or one major feature with at least two minor features.</p>
            </sec>
            <sec id="sec10">
                <title>Eligibility criteria</title>
                <p>Adults aged 18&#x00a0;years or older attending the AVBRH outpatient department with clinically suspected cutaneous lichen planus and willing to provide written informed consent will be considered eligible. Patients with isolated mucosal, genital, or scalp lichen planus will be excluded. Patients who have received topical or systemic treatment likely to alter lesional morphology within one month prior to enrolment will also be excluded.</p>
            </sec>
            <sec id="sec11">
                <title>Participant recruitment and lesion selection</title>
                <p>Potentially eligible participants will be recruited consecutively from the dermatology outpatient department during the study period. After clinical evaluation and written informed consent, one representative cutaneous lesion planned for punch biopsy will be selected for dermoscopic examination, UVFD assessment, and histopathological correlation. Dermoscopic and UVFD assessments will be performed before biopsy.</p>
            </sec>
            <sec id="sec12">
                <title>Study procedure</title>
                <p>For each enrolled participant, demographic and clinical details will be recorded in a structured proforma. The selected lesion will undergo dermoscopic examination and ultraviolet-induced fluorescence dermoscopic assessment. Images will be captured and archived for analysis. A provisional dermoscopic impression will be recorded before biopsy. Punch biopsy will then be performed from the same representative lesion, and the specimen will be processed for histopathological examination. Dermoscopic, UVFD, and histopathological findings will subsequently be correlated.</p>
            </sec>
            <sec id="sec13">
                <title>Blinding</title>
                <p>Dermoscopic and UVFD findings will be documented before histopathological examination. Wherever feasible, the histopathologist will be blinded to the dermoscopic and UVFD impressions at the time of histopathological assessment to minimise observer bias.</p>
            </sec>
        </sec>
        <sec id="sec14">
            <title>Sample size and statistical analysis</title>
            <sec id="sec15">
                <title>Sample size</title>
                <p>Published data specifically addressing the diagnostic accuracy of dermoscopy in cutaneous lichen planus are limited. Therefore, a pragmatic minimum sample size of 96 participants has been planned for this prospective observational study. This estimate was derived using a prevalence-based approach as an initial planning method, while acknowledging that prevalence-based calculations are not the ideal method for diagnostic accuracy studies. Because robust epidemiologic data for cutaneous lichen planus are scarce, published prevalence estimates for oral lichen planus were used as a proxy during protocol development, based on the systematic review by Gonz&#x00e1;lez-Moles et al.
                    <sup>
                        <xref ref-type="bibr" rid="ref3">3</xref>
                    </sup> This limitation is acknowledged, and the assumptions underlying the sample size will be revisited during the conduct of the study. The sample size estimation approach is illustrated in 
                    <xref ref-type="fig" rid="f4">
Figure 4</xref>.</p>
                <fig fig-type="figure" id="f4" orientation="portrait" position="float">
                    <label>
Figure 4. </label>
                    <caption>
                        <title>Diagram illustrating the formula used for sample size estimation.</title>
                    </caption>
                    <graphic id="gr4" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/197960/3b375550-b094-40c9-bca5-5c53c9d22817_figure4.gif"/>
                </fig>
            </sec>
            <sec id="sec16">
                <title>Statistical analysis</title>
                <p>All analyses will be conducted using R version 4.3.2. Continuous variables will be summarised using mean, standard deviation, median, minimum, and maximum values, as appropriate. Categorical variables will be summarised using counts and percentages.</p>
                <p>Histopathology will serve as the reference standard for the diagnosis of cutaneous lichen planus. The diagnostic performance of dermoscopy will be assessed by calculating sensitivity, specificity, positive predictive value, and negative predictive value, together with 95% confidence intervals where appropriate. Agreement between dermoscopic and histopathological findings will be evaluated using percentage agreement and the kappa statistic.
                    <sup>
                        <xref ref-type="bibr" rid="ref19">19</xref>
                    </sup> Receiver operating characteristic analysis and area under the curve will be used where applicable.
                    <sup>
                        <xref ref-type="bibr" rid="ref20">20</xref>
                    </sup>
                </p>
                <p>Categorical variables will be compared using the chi-square test or Fisher&#x2019;s exact test, as appropriate.
                    <sup>
                        <xref ref-type="bibr" rid="ref22">22</xref>
                    </sup> Continuous variables will be compared using the independent t-test or Wilcoxon Mann&#x2013;Whitney U test, depending on data distribution.
                    <sup>
                        <xref ref-type="bibr" rid="ref21">21</xref>
                    </sup> A p-value of less than 0.05 will be considered statistically significant.</p>
            </sec>
        </sec>
        <sec id="sec17">
            <title>Limitations</title>
            <p>

                <list list-type="order">
                    <list-item>
                        <label>1.</label>
                        <p>Correlation between dermoscopic and histopathological findings may be challenging because dermoscopy provides an axial surface view, whereas histopathology provides a cross-sectional tissue view.
                            <sup>
                                <xref ref-type="bibr" rid="ref23">23</xref>,
                                <xref ref-type="bibr" rid="ref24">24</xref>
                            </sup>
                        </p>
                    </list-item>
                    <list-item>
                        <label>2.</label>
                        <p>As this is a single-centre study conducted in central India, the study population may be relatively homogeneous, which may limit generalisability to other settings and skin phototypes. Future multicentre studies will be required for broader validation.</p>
                    </list-item>
                </list>
            </p>
        </sec>
        <sec id="sec18" sec-type="discussion">
            <title>Discussion</title>
            <p>
This study is expected to clarify the diagnostic utility of dermoscopy and ultraviolet-induced fluorescence dermoscopy in cutaneous lichen planus and to identify imaging features that correlate with histopathological findings. By exploring both conventional dermoscopic patterns and UVFD-derived observations, this protocol may contribute to the development of more refined non-invasive diagnostic approaches for lichen planus. The study&#x2019;s prospective design and planned clinicodermoscopic-histopathological correlation are strengths, although its single-centre setting may limit generalisability. The findings may also provide preliminary data to inform future multicentre validation studies.</p>
        </sec>
        <sec id="sec19">
            <title>Ethics and consent</title>
            <p>
This study has been approved by the Institutional Ethics Committee of Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, India (study approval number: DMIHER (DU)/IEC/2024/141; IEC Re-reg. No. ECR/440/Inst/MH/2013/RR-2019) in December 2023. Written informed consent will be obtained from all participants before enrolment into the study. Separate written consent will be obtained for the use of clinical images where applicable. The study will be conducted in accordance with the ethical principles of the Declaration of Helsinki.</p>
        </sec>
        <sec id="sec20">
            <title>Trial registration</title>
            <p>Clinical Trials Registry&#x2013;India (CTRI): CTRI/2025/05/086296; Reference No. REF/2024/03/080873. Registered on 05/05/2025 URL: 
                <ext-link ext-link-type="uri" xlink:href="https://ctri.nic.in/Clinicaltrials/regtrial.php?modid=1&amp;compid=19&amp;EncHid=71931.98915">https://ctri.nic.in/Clinicaltrials/regtrial.php?modid=1&amp;compid=19&amp;EncHid=71931.98915</ext-link>
            </p>
        </sec>
        <sec id="sec21">
            <title>Dissemination</title>
            <p>The study findings will be disseminated through publication in peer-reviewed journals and presentation at academic conferences.</p>
        </sec>
        <sec id="sec22">
            <title>Software availability</title>
            <p>Image analysis will be performed using ImageJ and QuPath. Statistical analysis will be conducted using R version 4.3.2. These are publicly available software tools. No custom source code was generated or used for this study protocol.</p>
        </sec>
        <sec id="sec23">
            <title>Use of generative AI and language tools</title>
            <p>During manuscript preparation, the authors used 
                <bold>OpenAI ChatGPT (GPT-5.4 Thinking)</bold>, 
                <bold>Google Gemini 3.1 Pro</bold>, and 
                <bold>Grammarly (Superhuman Go, running on OpenAI&#x2019;s GPT-4.1 family)</bold> solely to improve the English language, enhance readability, and cross-check journal author guidelines. These tools were not used for data generation, statistical analysis, interpretation of findings, or scientific decision-making. All generated suggestions were critically reviewed and edited by the authors, who take full responsibility for the final manuscript content.</p>
        </sec>
    </body>
    <back>
        <sec id="sec26">
            <title>Data availability</title>
            <sec id="sec27">
                <title>Primary data availability</title>
                <p>No primary data are associated with this article.</p>
            </sec>
            <sec id="sec28">
                <title>Extended data</title>
                <p>SPIRIT 2013 checklist for &#x201c;Illuminating diagnostic pathways: study protocol for a prospective observational study comparing inflammoscopy and ultraviolet-induced fluorescence dermoscopy with histopathology in cutaneous lichen planus&#x201d;. Zenodo. 
                    <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.5281/zenodo.19221491">https://doi.org/10.5281/zenodo.19221491</ext-link>. This project is available under the terms of the 
                    <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/publicdomain/zero/1.0/legalcode">Creative Commons Zero &#x201c;No rights reserved&#x201d; data waiver (CC0 1.0 Universal)</ext-link>.
                    <sup>
                        <xref ref-type="bibr" rid="ref25">25</xref>
                    </sup>
                </p>
            </sec>
            <sec id="sec29">
                <title>Reporting guidelines</title>
                <p>This study protocol has been prepared in accordance with relevant guidance for observational study protocols. A completed SPIRIT 2013 checklist for this study protocol has been deposited in Zenodo and is available at: 
                    <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.5281/zenodo.19221491">https://doi.org/10.5281/zenodo.19221491</ext-link>.</p>
            </sec>
        </sec>
        <ack>
            <title>Acknowledgements</title>
            <p>The authors thank the study participants, the Department of Biostatistics of DMIHER for statistical guidance, and the outpatient and ward nursing staff for their assistance during patient care and study procedures.</p>
        </ack>
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    </back>
    <sub-article article-type="reviewer-report" id="report484576">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.197960.r484576</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>&#x0160;piljak</surname>
                        <given-names>Bruno</given-names>
                    </name>
                    <xref ref-type="aff" rid="r484576a1">1</xref>
                    <role>Referee</role>
                </contrib>
                <aff id="r484576a1">
                    <label>1</label>University of Zagreb School of Dental Medicine, Zagreb, Croatia</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>27</day>
                <month>5</month>
                <year>2026</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2026 &#x0160;piljak B</copyright-statement>
                <copyright-year>2026</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport484576" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.179446.1"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>approve-with-reservations</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>Dear Authors, there are several methodological and conceptual concerns that must be addressed before the protocol can be deemed scientifically sound:</p>
            <p> Major comments:</p>
            <p> 1) The rationale is generally clear and relevant to clinical practice; however, the manuscript tends to exaggerate the expected diagnostic utility of UVFD, given the limited existing evidence specifically related to cutaneous lichen planus. The Introduction would benefit from a more explicit differentiation between evidence-based dermoscopic findings and the exploratory hypotheses surrounding UVFD. At present, some assertions regarding the anticipated superiority or additional value of UVFD remain speculative. Furthermore, the authors should more distinctly clarify whether the primary objective is to evaluate dermoscopy alone, UVFD alone, or the performance of combined dermoscopy and UVFD. Currently, the primary focus appears to be predominantly on dermoscopy, while the integration of UVFD throughout the manuscript is somewhat ambiguous.</p>
            <p> 2) The prospective observational design is suitable for the stated objectives. Nevertheless, several methodological aspects need clarification to enhance reproducibility: The manuscript does not adequately define how &#x201c;clinically suspected cutaneous lichen planus&#x201d; will be standardized among investigators. It remains unclear whether multiple dermatologists will assess lesions and if interobserver variability will be evaluated. The specifications of the dermoscopic equipment (including magnification, device type, UV wavelength, and polarized/non-polarized settings) should be elaborated upon in greater detail. Additionally, the UVFD acquisition protocol necessitates further standardization details, such as ambient lighting conditions, image capture distance, camera specifications, and fluorescence calibration procedures.&#x00a0;</p>
            <p> 3) The authors correctly utilize histopathology as the reference standard; however, the operational histopathological criteria outlined in the protocol seem somewhat arbitrary and lack validated scoring criteria. The justification for defining "two major features or one major feature with two minor features" should be supported by relevant references. Additionally, it should be clarified whether the histopathological evaluation will be conducted by a single dermatopathologist or by multiple observers.</p>
            <p> 4) The calculation of sample size represents a significant weakness in the protocol. The authors themselves recognize that prevalence-based calculations are not optimal for studies focused on diagnostic accuracy. This limitation considerably undermines methodological rigor. In diagnostic accuracy studies, the sample size should ideally be determined based on expected sensitivity/specificity, the precision of confidence intervals, and the anticipated prevalence among suspected lesions. The current estimation based on the prevalence of oral lichen planus as a surrogate is challenging to justify scientifically for cutaneous LP. The authors should either present a more robust calculation based on diagnostic accuracy or clearly define this study as an exploratory pilot protocol.</p>
            <p> 5) The proposed statistical methods are largely suitable, encompassing sensitivity, specificity, kappa statistics, ROC analysis, and confidence intervals. Nevertheless, ROC analysis may not be entirely relevant if the dermoscopic evaluation is binary or categorical instead of score-based. The manuscript must clarify the approach to handling missing data. There is no mention of adjustments for multiple comparisons, despite the presence of several secondary outcomes. The authors need to specify whether multivariable analysis will be taken into account if multiple dermoscopic variables are assessed concurrently.</p>
            <p> 6) The effort to blind histopathologists is praiseworthy; however, the phrase "wherever feasible" lacks precision. The protocol should clearly outline the circumstances under which blinding may not be possible, identify who will remain blinded, and confirm whether dermoscopic evaluators will also be blinded to histopathology during their assessments. The potential for incorporation bias should also be addressed, given that the same lesion is evaluated through clinical, dermoscopic, and histopathological methods.</p>
            <p> 7) The flowchart and structured forms are beneficial and enhance reproducibility. However, Figures 2 and 3 feature relatively complex tabular formats that may pose challenges for practical use without digital standardization. The classification of dermoscopic features could be improved by referencing established inflammoscopy terminology systems. UVFD findings are only slightly standardized in comparison to dermoscopic variables.</p>
            <p> 8) The Discussion section is succinct and generally well-balanced. The authors rightly recognize limitations associated with a single-center design and the challenges of correlating histopathology with dermoscopy. However, further limitations should be addressed: selection bias stemming from the inclusion of only patients willing to undergo biopsy, the exclusion of treated lesions, potential spectrum bias in the recruitment of patients from tertiary centers, and the restricted external validity across different skin phototypes.</p>
            <p> </p>
            <p> Minor comments:</p>
            <p> - The term "inflamoscopy" is used inconsistently in the manuscript, appearing as both "inflammoscopy" and "inflamoscopy."</p>
            <p> - Numerous grammatical and stylistic adjustments are required to enhance clarity.</p>
            <p> - The manuscript sometimes reiterates ideas related to Wickham striae and UV fluorescence.</p>
            <p> - The formatting of references needs to be meticulously checked for uniformity.</p>
            <p> - The authors should specify if lesions from various LP variants (such as hypertrophic, annular, actinic, etc.) will be examined individually.</p>
            <p> </p>
            <p> Best regards!</p>
            <p>Is the study design appropriate for the research question?</p>
            <p>Yes</p>
            <p>Is the rationale for, and objectives of, the study clearly described?</p>
            <p>Partly</p>
            <p>Are sufficient details of the methods provided to allow replication by others?</p>
            <p>Partly</p>
            <p>Are the datasets clearly presented in a useable and accessible format?</p>
            <p>Not applicable</p>
            <p>Reviewer Expertise:</p>
            <p>Oral medicine, oral pathology, dermatology-related oral manifestations, oral microbiology, salivary diagnostics, inflammatory diseases, oral potentially malignant disorders, head and neck oncology, dermoscopy-related mucosal diagnostics, biomaterials research, and translational clinical research.</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.</p>
        </body>
    </sub-article>
</article>
