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<journal-id journal-id-type="publisher-id">Front. Immunol.</journal-id>
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<journal-title>Frontiers in Immunology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Immunol.</abbrev-journal-title>
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<issn pub-type="epub">1664-3224</issn>
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<article-id pub-id-type="doi">10.3389/fimmu.2026.1753175</article-id>
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<subj-group subj-group-type="heading">
<subject>Case Report</subject>
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<title-group>
<article-title>Case Report: Periungual Xeligekimab injection for refractory Acrodermatitis continua of Hallopeau</article-title>
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<contrib contrib-type="author" equal-contrib="yes">
<name><surname>Cao</surname><given-names>Peng</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="author-notes" rid="fn003"><sup>&#x2020;</sup></xref>
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<name><surname>Yuan</surname><given-names>Aijie</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
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<name><surname>Yang</surname><given-names>Jingchen</given-names></name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
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<contrib contrib-type="author">
<name><surname>Zhang</surname><given-names>Yuning</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
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<name><surname>Guo</surname><given-names>Tao</given-names></name>
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<contrib contrib-type="author" corresp="yes">
<name><surname>Li</surname><given-names>Chen</given-names></name>
<xref ref-type="aff" rid="aff4"><sup>4</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>*</sup></xref>
<xref ref-type="author-notes" rid="fn004"><sup>&#x2021;</sup></xref>
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<aff id="aff1"><label>1</label><institution>Department of Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital</institution>, <city>Tianjin</city>,&#xa0;<country country="cn">China</country></aff>
<aff id="aff2"><label>2</label><institution>Graduate School, Tianjin University of Traditional Chinese Medicine</institution>, <city>Tianjin</city>,&#xa0;<country country="cn">China</country></aff>
<aff id="aff3"><label>3</label><institution>School of Nursing, Beijing University of Chinese Medicine</institution>, <city>Beijing</city>,&#xa0;<country country="cn">China</country></aff>
<aff id="aff4"><label>4</label><institution>Department of Dermatology, Tianjin Institute of Integrative Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital</institution>, <city>Tianjin</city>,&#xa0;<country country="cn">China</country></aff>
<author-notes>
<corresp id="c001"><label>*</label>Correspondence: Chen Li, <email xlink:href="mailto:casio1981@163.com">casio1981@163.com</email></corresp>
<fn fn-type="equal" id="fn003">
<p>&#x2020;These authors have contributed equally to this work</p></fn>
<fn fn-type="other" id="fn004">
<p>&#x2021;ORCID: Chen Li, <uri xlink:href="https://orcid.org/0000-0002-8527-1680">orcid.org/0000-0002-8527-1680</uri></p></fn>
</author-notes>
<pub-date publication-format="electronic" date-type="pub" iso-8601-date="2026-03-03">
<day>03</day>
<month>03</month>
<year>2026</year>
</pub-date>
<pub-date publication-format="electronic" date-type="collection">
<year>2026</year>
</pub-date>
<volume>17</volume>
<elocation-id>1753175</elocation-id>
<history>
<date date-type="received">
<day>24</day>
<month>11</month>
<year>2025</year>
</date>
<date date-type="accepted">
<day>17</day>
<month>02</month>
<year>2026</year>
</date>
<date date-type="rev-recd">
<day>11</day>
<month>01</month>
<year>2026</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#xa9; 2026 Cao, Yuan, Yang, Zhang, Guo and Li.</copyright-statement>
<copyright-year>2026</copyright-year>
<copyright-holder>Cao, Yuan, Yang, Zhang, Guo and Li</copyright-holder>
<license>
<ali:license_ref start_date="2026-03-03">https://creativecommons.org/licenses/by/4.0/</ali:license_ref>
<license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License (CC BY)</ext-link>. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p>
</license>
</permissions>
<abstract>
<p>This case report presents the novel and successful use of periungual Xeligekimab injections for managing refractory Acrodermatitis Continua of Hallopeau (ACH), representing the first documented application of this localized administration route for the IL-17A inhibitor. It contributes to the scientific literature by demonstrating a promising alternative therapeutic strategy for treatment-resistant ACH, highlighting the potential for enhanced local efficacy and minimized systemic exposure. The patient was a 36-year-old woman with a two-decade history of ACH affecting her digits, characterized by persistent periungual and subungual erythema, sterile pustules, significant nail plate dystrophy with thickening and fragmentation, and associated digital swelling, tenderness, and restricted motion. Prior therapies, including topical corticosteroids, phototherapy, and systemic tofacitinib, had proven ineffective. Diagnosis was confirmed clinically and supported by MRI, which revealed active bone marrow edema in the distal phalanges. The therapeutic intervention involved initial periungual injections of a diluted Xeligekimab formulation, which led to partial improvement. This was followed by a series of injections using undiluted Xeligekimab (100 mg/mL). This escalation resulted in marked clinical resolution: complete clearance of pustules and inflammation, healthy nail regrowth, and resolution of digital swelling and pain. Concurrently, the Dermatology Life Quality Index and pain scores dramatically improved, and follow-up MRI showed substantial resolution of the underlying bone marrow edema, confirming the treatment&#x2019;s efficacy on both cutaneous and deep osseous inflammation.</p>
</abstract>
<kwd-group>
<kwd>acrodermatitis continua of Hallopeau</kwd>
<kwd>case report</kwd>
<kwd>IL-17</kwd>
<kwd>periungual injection</kwd>
<kwd>xeligekimab</kwd>
</kwd-group>
<funding-group>
<funding-statement>The author(s) declared that financial support was received for this work and/or its publication. This study was funded by Tianjin Key Medical Discipline Construction Project (Grant No. TJYXZDXK-3-027C).</funding-statement>
</funding-group>
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<custom-meta-group>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders</meta-value>
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</front>
<body>
<sec id="s1" sec-type="intro">
<title>Introduction</title>
<p>Acrodermatitis continua of Hallopeau (ACH) is a rare, chronic variant of pustular psoriasis. The disease is characterized by the development of sterile pustules around and beneath the nail, periungual inflammation, nail dystrophy, osteolysis of the distal phalanges, and progressive pain and atrophy of the affected digits. This localized form of pustular psoriasis predominantly affects the distal portions of the fingers and toes (<xref ref-type="bibr" rid="B1">1</xref>). Current management strategies usually follow the international treatment guidelines for psoriasis and include the administration of topical calcineurin inhibitors, phototherapy, and systemic agents such as methotrexate. In recent years, biologic therapies targeting the interleukin-17 (IL-17), IL-23, and IL-36 signaling pathways have shown significant efficacy in the treatment of refractory ACH (<xref ref-type="bibr" rid="B2">2</xref>, <xref ref-type="bibr" rid="B3">3</xref>). Here, we report a case of treatment-resistant ACH that was successfully managed using an innovative approach, periungual injection of Xeligekimab, resulting in substantial clinical improvement of the digital lesions.</p>
</sec>
<sec id="s2">
<title>Case presentation</title>
<p>A 36-year-old woman presented with a 20-year history of recurrent erythema and sterile pustules around the nail folds of the left ring finger and right thumb, which had progressed gradually to thickening, opacification, and fragmentation of the nail plate. Over the past year, she had developed persistent swelling, tenderness, and restricted motion of the affected digits. The patient had previously received prolonged topical corticosteroid therapy and phototherapy without lasting improvement. Treatment with the Janus kinase (JAK) inhibitor tofacitinib for six months at another institution had failed to control the disease, with worsening of the symptoms. She denied any personal or family history of psoriasis or autoimmune disorders.</p>
<p>Dermatological examination revealed persistent periungual and subungual erythema and pustules involving the distal phalanges of the left ring finger and right thumb. The nail plates appeared thickened, opaque, longitudinally ridged, and fragmented, with marked dystrophy with partial nail loss. The affected digits exhibited diffuse fusiform swelling, marked tenderness, mildly elevated skin temperature, and limited passive flexion and extension (<xref ref-type="fig" rid="f1"><bold>Figure&#xa0;1a</bold></xref>). The Dermatology Life Quality Index (DLQI) score was 18/30, while the Visual Analogue Scale (VAS) pain score was 8/10. Given the presence of marked periungual swelling and pain, magnetic resonance imaging (MRI) was performed to exclude local infection or inflammatory osteitis. The MRI findings showed patchy T2/STIR hyperintensity and T1 hypointensity within the distal phalanges of the left ring finger, right ring finger, and right little finger (<xref ref-type="fig" rid="f2"><bold>Figure&#xa0;2a</bold></xref>), consistent with active bone marrow edema. As the patient was concerned that histopathological examination could further exacerbate tissue injury and therefore explicitly declined the procedure, the diagnosis of ACH was established based on the characteristic clinical features and MRI findings.</p>
<fig id="f1" position="float">
<label>Figure&#xa0;1</label>
<caption>
<p>Clinical presentation at baseline and after treatment with Xeligekimab.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fimmu-17-1753175-g001.tif">
<alt-text content-type="machine-generated">Three rows of sequential hand photographs display the progression of healing in fingernails over twenty weeks, with columns labeled as baseline, four, eight, twelve, sixteen, and twenty weeks, showing gradual improvement in nail condition and reduction of damage.</alt-text>
</graphic></fig>
<fig id="f2" position="float">
<label>Figure&#xa0;2</label>
<caption>
<p>MRI findings at baseline and after treatment with Xeligekimab. The post-treatment COR T2WI-FS sequence indicated marked improvement and partial resolution of the bone-marrow edema in the distal phalanges of the left fourth and right fourth and fifth fingers.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fimmu-17-1753175-g002.tif">
<alt-text content-type="machine-generated">Four-panel MRI graphic of hands labeled “a” and “b” at the bottom, showing finger bone structures. Red arrows indicate abnormalities at several fingertips on each hand consistent with pathological changes. Black background.</alt-text>
</graphic></fig>
<p>The first four treatment sessions involved a conservative dosing approach based on injection protocols for nail psoriasis (<xref ref-type="bibr" rid="B4">4</xref>). A five-fold dilution of Xeligekimab (100 mg/mL) was prepared by mixing 0.2 mL of the drug with 0.8 mL of normal saline, and 0.1 mL of the diluted solution was injected periungually into both affected digits at two-week intervals. By week 4, the pustules and erythema appeared somewhat reduced, although there was no improvement in the nail growth. By week 8, there were no new pustules, the periungual inflammation had subsided, and the digital swelling was slightly reduced; meanwhile, the DLQI score decreased to 14/30 and the VAS pain score dropped to 5/10.</p>
<p>Starting from the fifth treatment session, undiluted Xeligekimab (0.1 mL) was injected directly into each affected fingertip at two-week intervals, for a total of 10 sessions. By week 12, marked reductions in nail thickening and fragmentation were observed, and healthy nail regrowth was evident. By week 20, the periungual inflammation had resolved completely, with only mild longitudinal ridging visible on the smooth new nail plates, while the digital swelling and tenderness were also fully resolved (<xref ref-type="fig" rid="f1"><bold>Figure&#xa0;1b</bold></xref>). The DLQI score had improved to 2/30, and the VAS pain score had decreased to 0/10. A follow-up MRI showed substantially reduced T2/STIR hyperintensity at the previously affected sites of the distal phalanges (<xref ref-type="fig" rid="f2"><bold>Figure&#xa0;2b</bold></xref>), indicating significant resolution of the bone marrow edema and near-complete remission of the soft tissue swelling. No local adverse reactions, such as pain, necrosis, infection, or neuropathy, nor any other adverse events, were observed during the course of treatment and follow-up period.</p>
</sec>
<sec id="s3" sec-type="discussion">
<title>Discussion</title>
<p>This report is the first description of the successful treatment of refractory ACH using periungual injection of Xeligekimab. ACH, a rare variant of pustular psoriasis, is characterized by the presence of recurrent sterile pustules that can cause severe pain and irreversible destruction of the nails. Xeligekimab is a fully human monoclonal antibody that targets interleukin-17A (IL-17A). The antibody binds selectively to IL-17A, preventing its interaction with the IL-17A receptor complex and the consequent downstream release of pro-inflammatory cytokines and chemokines, thereby attenuating inflammation (<xref ref-type="bibr" rid="B5">5</xref>). Its efficacy and safety have been well-established in patients with moderate-to-severe plaque psoriasis and generalized pustular psoriasis (<xref ref-type="bibr" rid="B6">6</xref>, <xref ref-type="bibr" rid="B7">7</xref>). A review of the literature identified 12 reported cases of ACH treated with IL-17 inhibitors (<xref ref-type="table" rid="T1"><bold>Table&#xa0;1</bold></xref>), including seven treated with Secukinumab (<xref ref-type="bibr" rid="B8">8</xref>&#x2013;<xref ref-type="bibr" rid="B14">14</xref>), two with Ixekizumab (<xref ref-type="bibr" rid="B15">15</xref>, <xref ref-type="bibr" rid="B16">16</xref>) and three with Brodalumab (<xref ref-type="bibr" rid="B17">17</xref>&#x2013;<xref ref-type="bibr" rid="B19">19</xref>). The treatment durations ranged from 1 to 53 months. Collectively, these studies indicated that IL-17 blockade, either as monotherapy or in combination regimens, was effective in alleviating ACH. However, previous treatments have mostly used systemic administration of biologic agents at standard doses. Compared with the use of systemic biologics at standard doses, local injection of biologic agents is more targeted, faster, and safer (<xref ref-type="bibr" rid="B4">4</xref>, <xref ref-type="bibr" rid="B20">20</xref>&#x2013;<xref ref-type="bibr" rid="B22">22</xref>). Local periungual injection may provide more effective antibody delivery to the target site through direct diffusion and interstitial fluid movement, thereby avoiding the need for high systemic concentrations and reducing both costs and adverse effects (<xref ref-type="bibr" rid="B20">20</xref>).</p>
<table-wrap id="T1" position="float">
<label>Table&#xa0;1</label>
<caption>
<p>Literature reports of patients with ACH treated with IL-17 inhibitors.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="middle" align="left">Authors</th>
<th valign="middle" align="left">Age (Years)/Sex</th>
<th valign="middle" align="left">Biologic drug</th>
<th valign="middle" align="left">Combination drugs</th>
<th valign="middle" align="left">Dosage schedule</th>
<th valign="middle" align="left">Outcome</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="middle" align="left">Galluzzo M et&#xa0;al (<xref ref-type="bibr" rid="B8">8</xref>)</td>
<td valign="middle" align="left">27/Female</td>
<td valign="middle" align="left">Secukinumab</td>
<td valign="middle" align="left">/</td>
<td valign="middle" align="left">52 weeks of treatment;<break/>300 mg by subcutaneous injection at weeks 0, 1, 2, 3, 4 and every 4 weeks thereafter</td>
<td valign="middle" align="left">Success</td>
</tr>
<tr>
<td valign="middle" align="left">Muggli D et&#xa0;al (<xref ref-type="bibr" rid="B10">10</xref>)</td>
<td valign="middle" align="left">87/Male</td>
<td valign="middle" align="left">Secukinumab</td>
<td valign="middle" align="left">/</td>
<td valign="middle" align="left">6 weeks of treatment;<break/>300 mg by subcutaneous injection at weeks 0, 1, 2, 3, 4 and every 4 weeks thereafter</td>
<td valign="middle" align="left">Success</td>
</tr>
<tr>
<td valign="middle" align="left">Khosravi-Hafshejani T et&#xa0;al (<xref ref-type="bibr" rid="B11">11</xref>)</td>
<td valign="middle" align="left">53/Male</td>
<td valign="middle" align="left">Secukinumab</td>
<td valign="middle" align="left">/</td>
<td valign="middle" align="left">2 years of treatment;<break/>unknown</td>
<td valign="middle" align="left">Success</td>
</tr>
<tr>
<td valign="middle" align="left">Balestri R et&#xa0;al (<xref ref-type="bibr" rid="B12">12</xref>)</td>
<td valign="middle" align="left">43/Male</td>
<td valign="middle" align="left">Secukinumab</td>
<td valign="middle" align="left">Acitretin for 4 weeks</td>
<td valign="middle" align="left">10 months of treatment;<break/>300 mg by subcutaneous injection at weeks 0, 1, 2, 3, 4 and every 4 weeks thereafter</td>
<td valign="middle" align="left">Success</td>
</tr>
<tr>
<td valign="middle" align="left">Baron JA (<xref ref-type="bibr" rid="B13">13</xref>)</td>
<td valign="middle" align="left">42/Female</td>
<td valign="middle" align="left">Secukinumab</td>
<td valign="middle" align="left">/</td>
<td valign="middle" align="left">1 month of treatment;<break/>300 mg by subcutaneous injection at weeks 0, 1, 2, 3, 4</td>
<td valign="middle" align="left">Success</td>
</tr>
<tr>
<td valign="middle" align="left">Yao XY et&#xa0;al (<xref ref-type="bibr" rid="B14">14</xref>)</td>
<td valign="middle" align="left">44/Male</td>
<td valign="middle" align="left">Secukinumab</td>
<td valign="middle" align="left">Apremilast 60mg/day after 2 years of Secukinumab<break/>treatment</td>
<td valign="middle" align="left">4 years and 5 months of treatment;<break/>300 mg by subcutaneously every 4 weeks for 2 years, then (post-combination therapy) every 4 weeks for 5 months and every 8 weeks thereafter</td>
<td valign="middle" align="left">Success</td>
</tr>
<tr>
<td valign="middle" align="left">Miller AC et&#xa0;al (<xref ref-type="bibr" rid="B15">15</xref>)</td>
<td valign="middle" align="left">31/Female</td>
<td valign="middle" align="left">ixekizumab</td>
<td valign="middle" align="left">/</td>
<td valign="middle" align="left">3 months of treatment;<break/>80 mg by subcutaneous injection every 2 weeks</td>
<td valign="middle" align="left">Success</td>
</tr>
<tr>
<td valign="middle" align="left">Battista T et&#xa0;al (<xref ref-type="bibr" rid="B16">16</xref>)</td>
<td valign="middle" align="left">72/Male</td>
<td valign="middle" align="left">ixekizumab</td>
<td valign="middle" align="left">/</td>
<td valign="middle" align="left">7 months of treatment;<break/>160 mg by subcutaneous injection at weeks 0 and 80 mg every 2 weeks thereafter</td>
<td valign="middle" align="left">Success</td>
</tr>
<tr>
<td valign="middle" align="left">Milani-Nejad N et&#xa0;al (<xref ref-type="bibr" rid="B17">17</xref>)</td>
<td valign="middle" align="left">60/Male</td>
<td valign="middle" align="left">Brodalumab</td>
<td valign="middle" align="left">/</td>
<td valign="middle" align="left">6 months of treatment;<break/>210 mg by subcutaneous injection at weeks 0, 1, 2 and every 2 weeks thereafter</td>
<td valign="middle" align="left">Success</td>
</tr>
<tr>
<td valign="middle" align="left">Passante M et&#xa0;al (<xref ref-type="bibr" rid="B18">18</xref>)</td>
<td valign="middle" align="left">37/Female</td>
<td valign="middle" align="left">Brodalumab</td>
<td valign="middle" align="left">/</td>
<td valign="middle" align="left">6 months of treatment;<break/>210 mg by subcutaneous injection at weeks 0, 1, 2 and every 2 weeks thereafter</td>
<td valign="middle" align="left">Success</td>
</tr>
<tr>
<td valign="middle" align="left">Bardazzi F et&#xa0;al (<xref ref-type="bibr" rid="B19">19</xref>)</td>
<td valign="middle" align="left">43/Male</td>
<td valign="middle" align="left">Brodalumab</td>
<td valign="middle" align="left">/</td>
<td valign="middle" align="left">12 months of treatment;<break/>210 mg by subcutaneous injection at weeks 1, 2, 3 and every 2 weeks thereafter</td>
<td valign="middle" align="left">Success</td>
</tr>
</tbody>
</table>
</table-wrap>
<p>A study by He et&#xa0;al. describes the treatment of patients with nail psoriasis with intralesional injections of Secukinumab at concentrations of 7.5, 15, and 30 mg/mL for 12 weeks. All three concentrations resulted in significant clinical improvement, and the sustained local accumulation of the drug extended the duration of the prolonged the post-treatment benefit (<xref ref-type="bibr" rid="B23">23</xref>). In the present case, the initial four injections represented a diluted formulation (20 mg/mL), leading to reductions of 22.2% and 37.5% in the DLQI and VAS score, respectively, by week 8. Subsequent treatment with undiluted Xeligekimab resulted in further improvement, with decreases in the DLQI and VAS scores of 85.7% and 100%, respectively, by week 20 compared with week 8. These findings suggest that for complex, treatment-refractory ACH, higher local drug concentrations may induce more rapid and durable responses; however, optimal dosing and safety thresholds require further investigation in controlled studies.</p>
<p>ACH is often accompanied by various changes in bone, including hyperostosis, bone resorption, erosion, and secondary osteomyelitis. Excessive activation of inflammatory mediators may also induce arthritis and bone-marrow alterations. Chronic cutaneous inflammation can extend into adjacent bone tissues, where inflammatory cytokines can disrupt vascular permeability and induce exudation, mediated by hematogenous or direct diffusion pathways. Moreover, ACH may impair the regulation of local neurovascular functions, leading to vasomotor dysfunction and venous stasis that can further exacerbate the bone-marrow edema (<xref ref-type="bibr" rid="B24">24</xref>). Although certain small, lipophilic topical agents can penetrate the superficial dermis, even advanced transdermal delivery systems, such as nano-carriers or penetration enhancers, are rarely associated with effective drug concentrations beyond the dermal layer, limiting their efficacy in counteracting deep inflammatory processes such as bone-marrow edema (<xref ref-type="bibr" rid="B25">25</xref>). In the present case, the MRI findings revealed marked edema of the bone marrow in the distal phalanges, consistent with inflammatory osteitis. Following periungual injection of Xeligekimab, the bone-marrow edema resolved substantially, indicating that localized high-concentration IL-17 blockade is effective in modulating deep inflammatory activity extending from the skin to the bone.</p>
</sec>
<sec id="s4" sec-type="conclusions">
<title>Conclusion</title>
<p>Periungual injection of Xeligekimab at a concentration of 100 mg/mL may represent one of the potential optimal treatment options for ACH. However, this study has several limitations. First, as a single-patient case report, statistical quantification is difficult, and the findings cannot be generalized to the broader ACH patient population. Second, the lack of long-term follow-up data precludes assessment of the long-term efficacy and safety of this treatment regimen. In addition, the absence of pharmacokinetic data prevented a precise characterization of the drug distribution profile of Xeligekimab and did not allow further optimization of the dosing strategy. Finally, the potential risks of high concentration periungual biologic injections should not be overlooked, including but not limited to infection, bleeding, nerve injury, and pain, as well as safety issues inherent to the biologic agents themselves.</p>
</sec>
</body>
<back>
<sec id="s5" sec-type="data-availability">
<title>Data availability statement</title>
<p>The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/supplementary material.</p></sec>
<sec id="s6" sec-type="ethics-statement">
<title>Ethics statement</title>
<p>The studies involving humans were approved by The Ethics Committee of the Affiliated Hospital of Tianjin Academy of Traditional Chinese Medicine. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.</p></sec>
<sec id="s7" sec-type="author-contributions">
<title>Author contributions</title>
<p>PC: Writing &#x2013; review &amp; editing, Writing &#x2013; original draft. AY: Writing &#x2013; review &amp; editing, Writing &#x2013; original draft. JY: Writing &#x2013; original draft, Writing &#x2013; review &amp; editing. YZ: Writing &#x2013; review &amp; editing. TG: Writing &#x2013; review &amp; editing. CL: Funding acquisition, Project administration, Resources, Writing &#x2013; review &amp; editing.</p></sec>
<sec id="s9" sec-type="COI-statement">
<title>Conflict of interest</title>
<p>The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p></sec>
<sec id="s10" sec-type="ai-statement">
<title>Generative AI statement</title>
<p>The author(s) declared that generative AI was not used in the creation of this manuscript.</p>
<p>Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.</p></sec>
<sec id="s11" sec-type="disclaimer">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p></sec>
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<p>Edited by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/2244552">Emmanouil Karampinis</ext-link>, University of Thessaly, Greece</p></fn>
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<p><ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/3295606">Olga Toli</ext-link>, Aristotle University of Thessaloniki, Greece</p></fn>
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