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  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">126</journal-id>
      <journal-id journal-id-type="index">urn:lsid:arphahub.com:pub:7099c1e0-efdc-54e4-93b7-b6ecd3612deb</journal-id>
      <journal-title-group>
        <journal-title xml:lang="en">Bulgarian Society of Medical Sciences Journal</journal-title>
        <abbrev-journal-title xml:lang="en">BSMS</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">2815-4959</issn>
      <publisher>
        <publisher-name>Nora 2000</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="doi">10.3897/bsms.4.121275</article-id>
      <article-id pub-id-type="publisher-id">121275</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Case Report</subject>
        </subj-group>
        <subj-group subj-group-type="scientific_subject">
          <subject>Orthopedic surgery</subject>
          <subject>Pediatrics</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>﻿Extrapulmonary forms of tuberculosis. Clinical case report of a child with tuberculous osteoarthritis</article-title>
      </title-group>
      <contrib-group content-type="authors">
        <contrib contrib-type="author" corresp="yes">
          <name name-style="western">
            <surname>Pavlov</surname>
            <given-names>Petar</given-names>
          </name>
          <email xlink:type="simple">pepi.antonov.94@abv.bg</email>
          <xref ref-type="aff" rid="A1">1</xref>
          <role content-type="http://credit.niso.org/contributor-roles/writing-original-draft/">Writing - original draft</role>
        </contrib>
        <contrib contrib-type="author" corresp="no">
          <name name-style="western">
            <surname>Stefanov</surname>
            <given-names>Stefan</given-names>
          </name>
          <xref ref-type="aff" rid="A2">2</xref>
          <role content-type="http://credit.niso.org/contributor-roles/writing-review-editing/">Writing - review and editing</role>
        </contrib>
        <contrib contrib-type="author" corresp="no">
          <name name-style="western">
            <surname>Pukalski</surname>
            <given-names>Yavor</given-names>
          </name>
          <xref ref-type="aff" rid="A3">3</xref>
          <role content-type="http://credit.niso.org/contributor-roles/writing-review-editing/">Writing - review and editing</role>
        </contrib>
        <contrib contrib-type="author" corresp="no">
          <name name-style="western">
            <surname>Vasilev</surname>
            <given-names>Teodor</given-names>
          </name>
          <uri content-type="orcid">https://orcid.org/0000-0002-3509-1841</uri>
          <xref ref-type="aff" rid="A2">2</xref>
          <role content-type="http://credit.niso.org/contributor-roles/data-curation/">Data curation</role>
        </contrib>
      </contrib-group>
      <aff id="A1">
        <label>1</label>
        <addr-line content-type="verbatim">Clinic of Child Pulmonary Diseases and Tuberculosis of University Hospital “St. Ivan Rilski”, Sofia, Sofia, Bulgaria</addr-line>
        <institution>University Hospital “St. Ivan Rilski”</institution>
        <addr-line content-type="city">Sofia</addr-line>
        <country>Bulgaria</country>
      </aff>
      <aff id="A2">
        <label>2</label>
        <addr-line content-type="verbatim">Rheumatology Clinic of The Pediatric Hospital “Prof. Ivan Mitev”, Sofia, Sofia, Bulgaria</addr-line>
        <institution>Pediatric Hospital "Prof. Ivan Mitev"</institution>
        <addr-line content-type="city">Sofia</addr-line>
        <country>Bulgaria</country>
      </aff>
      <aff id="A3">
        <label>3</label>
        <addr-line content-type="verbatim">Pediatric Surgery Clinic of UMHATEM “N. I. Pirogov”, Sofia, Sofia, Bulgaria</addr-line>
        <institution>UMHATEM "N. I. Pirogov"</institution>
        <addr-line content-type="city">Sofia</addr-line>
        <country>Bulgaria</country>
      </aff>
      <author-notes>
        <fn fn-type="corresp">
          <p>Corresponding author: Petar Pavlov; E-mail: <email xlink:type="simple">pepi.antonov.94@abv.bg</email></p>
        </fn>
      </author-notes>
      <pub-date pub-type="collection">
        <year>2024</year>
      </pub-date>
      <pub-date pub-type="epub">
        <day>05</day>
        <month>08</month>
        <year>2024</year>
      </pub-date>
      <volume>4</volume>
      <elocation-id>e121275</elocation-id>
      <uri content-type="arpha" xlink:href="http://openbiodiv.net/0EE896D6-7405-54FB-AFC9-8BB2C4E9A4FE">0EE896D6-7405-54FB-AFC9-8BB2C4E9A4FE</uri>
      <uri content-type="zenodo_dep_id" xlink:href="https://zenodo.org/record/13234262">13234262</uri>
      <history>
        <date date-type="received">
          <day>20</day>
          <month>02</month>
          <year>2024</year>
        </date>
        <date date-type="accepted">
          <day>15</day>
          <month>04</month>
          <year>2024</year>
        </date>
      </history>
      <permissions>
        <copyright-statement>Petar Pavlov, Stefan Stefanov, Yavor Pukalski, Teodor Vasilev</copyright-statement>
        <license license-type="creative-commons-attribution" xlink:href="http://creativecommons.org/licenses/by/4.0/" xlink:type="simple">
          <license-p>This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
        </license>
      </permissions>
      <abstract>
        <label>﻿Abstract</label>
        <p><bold>Introduction</bold>: Tuberculous osteoarthritis, caused by Mycobacterium tuberculosis, is a very rare extrapulmonary manifestation of tuberculosis, especially in children.</p>
        <p><bold>Aim</bold>: This article presents a clinical case of a 21-month-old male patient with tuberculous osteoarthritis affecting the ankle joint. The rarity of this pathology underscores the critical importance of swift diagnosis and a multidisciplinary approach involving specialists from diverse medical fields.</p>
        <p><bold>Results</bold>: Early initiation of specific antituberculous treatment, coupled with timely surgical intervention, ameliorated the patient’s immediate suffering. Furthermore, this combined therapeutic strategy holds promise for a favorable long-term prognosis regarding joint function.</p>
        <p><bold>Conclusion</bold>: Tuberculosis in children exhibits markedly diminished incidence, and its extrapulmonary variants are exceedingly rare. However, clinicians should maintain a high index of suspicion, particularly when confronted with recalcitrant diseases that defy conventional therapeutic approaches. A comprehensive understanding of tuberculous osteoarthritis, despite its rarity, is pivotal for effective management.</p>
      </abstract>
      <kwd-group>
        <label>Keywords</label>
        <kwd>tuberculosis</kwd>
        <kwd>osteoarthritis</kwd>
        <kwd>pediatric disease</kwd>
        <kwd>pediatric surgery</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="﻿Introduction" id="SECID0ENE">
      <title>﻿Introduction</title>
      <p>Tuberculosis (<abbrev xlink:title="Tuberculosis" id="ABBRID0ETE">TB</abbrev>), caused by Mycobacterium tuberculosis, remains a formidable global health challenge. Despite concerted efforts by medical experts worldwide, <abbrev xlink:title="Tuberculosis" id="ABBRID0EXE">TB</abbrev> continues to afflict approximately one-third of the world’s population, with 10% of infected individuals progressing to active tuberculosis disease during their lifetimes. Alongside HIV/AIDS and malaria, <abbrev xlink:title="Tuberculosis" id="ABBRID0E2E">TB</abbrev> stands as a critical health priority of the 21<sup>st</sup> century [<xref ref-type="bibr" rid="B1">1</xref>].</p>
      <p>According to Prof. Petko Minchev, Tuberculosis is a monoetiological disease with polymorphological manifestations. The disease can affect various organs and systems within the human body [<xref ref-type="bibr" rid="B1">1</xref>]. These diverse presentations can be broadly categorized into two main groups: pulmonary and extrapulmonary forms of tuberculosis (Tab. <xref ref-type="table" rid="T1">1</xref>). While pulmonary <abbrev xlink:title="Tuberculosis" id="ABBRID0EPF">TB</abbrev> garners significant attention, extrapulmonary forms, such as tuberculous osteoarthritis, remain less common but equally significant [<xref ref-type="bibr" rid="B2">2</xref>].</p>
      <table-wrap id="T1" position="float" orientation="portrait">
        <label>Table 1.</label>
        <caption>
          <p>Different forms of <abbrev xlink:title="Tuberculosis" id="ABBRID0ENDAC">TB</abbrev> disease in childhood.</p>
        </caption>
        <table id="TID0EGGAC" rules="all">
          <tbody>
            <tr>
              <td rowspan="1" colspan="2" style="color: #231f20">
                <bold>Forms of Tuberculous disease in childhood</bold>
              </td>
            </tr>
            <tr>
              <td rowspan="1" colspan="1" style="color: #231f20">
                <bold>Pulmonary forms of <abbrev xlink:title="Tuberculosis" id="ABBRID0EFEAC">TB</abbrev></bold>
              </td>
              <td rowspan="1" colspan="1" style="color: #231f20">
                <bold>Extrapulmonary forms of <abbrev xlink:title="Tuberculosis" id="ABBRID0EQEAC">TB</abbrev></bold>
              </td>
            </tr>
            <tr>
              <td rowspan="1" colspan="1" style="color: #231f20">Primary <abbrev xlink:title="Tuberculosis" id="ABBRID0E1EAC">TB</abbrev> complex</td>
              <td rowspan="1" colspan="1" style="color: #231f20"><abbrev xlink:title="Tuberculosis" id="ABBRID0EDFAC">TB</abbrev> meningoencephalitis</td>
            </tr>
            <tr>
              <td rowspan="1" colspan="1" style="color: #231f20">Intrathoracic tuberculous lymphadenopathy</td>
              <td rowspan="1" colspan="1" style="color: #231f20">Peripheral tuberculous lymphadenopathy</td>
            </tr>
            <tr>
              <td rowspan="1" colspan="1" style="color: #231f20">Infiltrative tuberculosis</td>
              <td rowspan="1" colspan="1" style="color: #231f20">Tuberculous pericarditis and myopericarditis</td>
            </tr>
            <tr>
              <td rowspan="1" colspan="1" style="color: #231f20">Caseous pneumonia</td>
              <td rowspan="1" colspan="1" style="color: #231f20">Genitourinary tuberculosis</td>
            </tr>
            <tr>
              <td rowspan="1" colspan="1" style="color: #231f20"><abbrev xlink:title="Tuberculosis" id="ABBRID0EIGAC">TB</abbrev> pleuritis</td>
              <td rowspan="1" colspan="1" style="color: #231f20">Ocular tuberculosis</td>
            </tr>
            <tr>
              <td rowspan="1" colspan="1" style="color: #231f20">Pulmonary tuberculoma</td>
              <td rowspan="1" colspan="1" style="color: #231f20">Skin tuberculosis</td>
            </tr>
            <tr>
              <td rowspan="1" colspan="1" style="color: #231f20">Miliary tuberculosis</td>
              <td rowspan="1" colspan="1" style="color: #231f20">Tuberculosis of bones and joints</td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
    </sec>
    <sec sec-type="﻿Case presentation" id="SECID0EXF">
      <title>﻿Case presentation</title>
      <p>Тhe Clinic of Child Pulmonary Diseases and Tuberculosis of University Hospital “St. Ivan Rilski” in Sofia, Bulgaria admitted a 21-month-old male patient. Born full-term and without complications in Germany, where BCG vaccination is not mandatory, the child currently resided in Bulgaria with his family. Notably, both his father and brother were treated for tuberculosis prior to the child’s birth. The boy’s presenting complaints, which emerged two weeks earlier, included fever reaching up to 39°C, edema, hyperemia, and pain localized in the area of his left ankle. Seeking medical attention, the parents promptly took him to a nearby healthcare facility, where he was subsequently hospitalized. Laboratory investigations revealed elevated inflammatory markers, while auscultation detected an exudative finding in the left hemithorax. A chest radiography confirmed pneumonic changes in the left apex, prompting initiation of standard antibiotic therapy. Additionally, the left ankle joint was punctured, and material was collected for microbiological examination, although no culture growth was observed. Despite a two-week course of treatment, the child’s fever persisted, and follow-up chest radiography indicated incomplete resorption of the previously described changes. In light of the differential diagnosis, tuberculosis was considered. Consequently, the medical team performed a Mantoux tuberculin skin test (resulting in a 9 mm dense infiltrate at the 72<sup>nd</sup> hour) and conducted a T.SPOT-<abbrev xlink:title="Tuberculosis" id="ABBRID0E6F">TB</abbrev> test, which yielded a positive result. As a result, the child was referred for specific treatment to the Clinic of Child Pulmonary Diseases and Tuberculosis of University Hospital “St. Ivan Rilski” in Sofia, Bulgaria.</p>
      <p>On admission, the child presented with stable general condition and was afebrile. Notably, no BCG-vaccine scar was discernible on his left shoulder. Respiratory examination revealed bilaterally vesicular breath sounds without wheezing. The left ankle exhibited swelling, characterized by a livid skin color, tenderness upon palpation, and restricted mobility. Laboratory investigations demonstrated elevated inflammatory markers, including a white blood cell count (WBC) of 14.8 x 10^9/l and an erythrocyte sedimentation rate of 30 mm/h. Furthermore, computed tomography revealed infiltrative changes within the left upper lung lobe and enlarged intrathoracic lymph nodes bilaterally (Fig. <xref ref-type="fig" rid="F1">1</xref>).</p>
      <p>The positive immunological test, specifically the T.SPOT-<abbrev xlink:title="Tuberculosis" id="ABBRID0ELG">TB</abbrev> assay, coupled with elevated inflammatory activity and the distinctive morphological alterations observed via chest computed tomography (<abbrev xlink:title="computed tomography" id="ABBRID0EPG">CT</abbrev>) collectively provided compelling grounds to initiate targeted anti-tuberculosis treatment. This therapeutic regimen encompassed the administration of Streptomycin, Rifampicin, and Isoniazid. Notably, despite exhaustive efforts, no etiological agent was successfully isolated from the gastric lavage tests.</p>
      <p>However, the persistent arthritis affecting the left ankle joint remained an enigma. In our pursuit of diagnostic clarity, several plausible entities were meticulously considered within the framework of differential diagnosis of left ankle arthritis (Fig. <xref ref-type="fig" rid="F2">2</xref>):</p>
      <list list-type="order">
        <list-item>
          <p>Juvenile Arthritis: Although this autoimmune condition is of minimal likelihood given the patient’s age and its tenuous association with tuberculosis, it was conscientiously evaluated.
</p>
        </list-item>
        <list-item>
          <p>Reactive Arthritis (Poncet’s Disease): This reactive inflammatory process, often triggered by an antecedent infection, was scrutinized as a potential culprit.
</p>
        </list-item>
        <list-item>
          <p>Septic Arthritis: The possibility of septic arthritis, characterized by joint inflammation secondary to microbial invasion, was meticulously weighed.
</p>
        </list-item>
        <list-item>
          <p>Tuberculous Osteoarthritis: Given the overarching context of tuberculosis, this form of joint involvement was a pertinent consideration.
</p>
        </list-item>
      </list>
      <p>To elucidate the child’s condition comprehensively, a consultation ensued with a pediatric rheumatologist affiliated with the Rheumatology Clinic of The Pediatric Hospital “Prof. Ivan Mitev” in Sofia, Bulgaria. During the meticulous physical examination and ultrasound assessment, synovitis within the left upper ankle joint was discerned. Subsequently, the child was referred to the Pediatric Surgery Clinic of UMHATEM “N. I. Pirogov” in Sofia, Bulgaria. Employing both echography and radiography, the evaluation of the affected joint unveiled several noteworthy findings – reduced bone density, fluid collections in the area of the fibular malleolus and an osteolytic zone (Fig. <xref ref-type="fig" rid="F3">3</xref>).</p>
      <p>Under general anesthesia a surgical incision in the area of the lateral malleolus was performed and the left talocrural joint was opened. Minimal amounts of purulent exudate and necrotic tissue were evacuated. A proximal penetration of the joint to the overlying bones was assessed. Histological and microbiological examinations were conducted. The operative site underwent rigorous lavage and sanitation using 0,9% saline, 10% hydrogen peroxide, sol. Hibitani and 7,5% povidone iodine, were carried out and the operative wound was closed. Subsequent to a period of vigilant observation, the pediatric patient was re-referred to The Clinic of Child Pulmonary Diseases and Tuberculosis of University Hospital “St. Ivan Rilski” in Sofia, Bulgaria. Unfortunately, the microbiological examination conducted during the surgical intervention failed to identify a definitive etiological agent. However, histology revealed the presence of necrotic tissue, inflammatory infiltrates, epithelioid cells, Langhans-type giant cells and hemorrhagic manifestations. These histopathological findings most robustly correlated with a diagnosis of tuberculous disease.</p>
      <p>Following extensive deliberation by medical specialists, it was determined that the patient’s anti-tuberculous therapy should be continuously administered. Over the subsequent month, notable improvements in the patient’s general condition, fever control, and weight gain were observed. However, at the close of December, approximately one month after the initial joint incision, a recurrence of symptoms manifested. Swelling, hyperemia, and pain reemerged in the area surrounding the same ankle. Consequently, the child was promptly referred once more to the Pediatric Surgery Clinic of UMHATEM “N. I. Pirogov”, Sofia, Bulgaria. During this subsequent surgical intervention, a meticulous debridement procedure was executed. Approximately 15 milliliters of purulent material were evacuated from within the joint and the vicinity around the fibula. Postoperatively, the local status of the ankle exhibited gradual improvement.</p>
      <p>In three months the wound had successfully healed with the emergence of granulation tissue at the site of the surgical intervention (Fig. <xref ref-type="fig" rid="F4">4</xref>). Subsequently, in 7 months of anti-tuberculosis treatment, only two scars remained visible from the performed manipulations (Fig. <xref ref-type="fig" rid="F5">5</xref>). Remarkably, in addition to the local healing process, the functionality of the affected joint was fully restored. The child regained the ability to step on the foot without pain, and a full range of motion in the ankle was once again possible.</p>
      <p>During the course of specific therapy, the child’s laboratory parameters exhibited a return to normalcy, signifying a favorable response to treatment. Furthermore, the follow-up chest radiography revealed a complete resorption of the previously observed infiltrative changes after 5 months of treatment (Fig. <xref ref-type="fig" rid="F6">6</xref>).</p>
      <fig id="F1" position="float" orientation="portrait">
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        <object-id content-type="arpha">AB7FD47D-EAB2-5E0C-AA9B-3E90D55D84A0</object-id>
        <label>Figure 1.</label>
        <caption>
          <p>Chest <abbrev xlink:title="computed tomography" id="ABBRID0EKHAC">CT</abbrev> – infiltrative changes in the left upper lung lobe and bilateral hilar lymphadenomegaly.</p>
        </caption>
        <graphic xlink:href="bsms-04-001_article-121275__-g001.jpg" position="float" orientation="portrait" xlink:type="simple" id="oo_1108567.jpg">
          <uri content-type="original_file">https://binary.pensoft.net/fig/1108567</uri>
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      <fig id="F2" position="float" orientation="portrait">
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        <object-id content-type="arpha">77145884-7FED-51E8-ADC1-EF77333C2C28</object-id>
        <label>Figure 2.</label>
        <caption>
          <p>Current condition of the ankle at the time of the child’s admission to the clinic.</p>
        </caption>
        <graphic xlink:href="bsms-04-001_article-121275__-g002.jpg" position="float" orientation="portrait" xlink:type="simple" id="oo_1108568.jpg">
          <uri content-type="original_file">https://binary.pensoft.net/fig/1108568</uri>
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      <fig id="F3" position="float" orientation="portrait">
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        <object-id content-type="arpha">9B4E9BD8-A58D-54EA-8309-310C7D68FC67</object-id>
        <label>Figure 3.</label>
        <caption>
          <p>X-ray of left ankle – osteolytic zone.</p>
        </caption>
        <graphic xlink:href="bsms-04-001_article-121275__-g003.jpg" position="float" orientation="portrait" xlink:type="simple" id="oo_1108569.jpg">
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      <fig id="F4" position="float" orientation="portrait">
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        <object-id content-type="arpha">FF2BFA55-9125-5915-89CE-1C232A29CB9F</object-id>
        <label>Figure 4.</label>
        <caption>
          <p>Wound healing with formation of granulation tissue.</p>
        </caption>
        <graphic xlink:href="bsms-04-001_article-121275__-g004.jpg" position="float" orientation="portrait" xlink:type="simple" id="oo_1108570.jpg">
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      </fig>
      <fig id="F5" position="float" orientation="portrait">
        <object-id content-type="doi">10.3897/bsms.4.121275.figure5</object-id>
        <object-id content-type="arpha">6054AFBB-4769-5124-9C07-51073669E25B</object-id>
        <label>Figure 5.</label>
        <caption>
          <p>Two scars from the conducted manipulations in the area of the left ankle.</p>
        </caption>
        <graphic xlink:href="bsms-04-001_article-121275__-g005.jpg" position="float" orientation="portrait" xlink:type="simple" id="oo_1108571.jpg">
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        <object-id content-type="arpha">EFD83D36-E3BD-5B3D-9335-FECCE98C67B4</object-id>
        <label>Figure 6.</label>
        <caption>
          <p>Chest X-ray from April 2023 – resorption of the infiltrative changes compared to <abbrev xlink:title="computed tomography" id="ABBRID0ELJAC">CT</abbrev> from November 2022.</p>
        </caption>
        <graphic xlink:href="bsms-04-001_article-121275__-g006.jpg" position="float" orientation="portrait" xlink:type="simple" id="oo_1108572.jpg">
          <uri content-type="original_file">https://binary.pensoft.net/fig/1108572</uri>
        </graphic>
      </fig>
    </sec>
    <sec sec-type="﻿Discussion" id="SECID0EXH">
      <title>﻿Discussion</title>
      <p>Tuberculosis of bones and joints represents a secondary form of the disease resulting from hematogenous dissemination originating from new or unhealed caseous foci within the lungs [<xref ref-type="bibr" rid="B3">3</xref>]. This hematogenous spread usually targets the richly blood-supplied middle part of long bones, subsequently affecting the nearby joint. While its incidence varies among different ethnic groups, with a frequency ranging from 0.2 to 16 cases per 100,000 population in South Asia [<xref ref-type="bibr" rid="B1">1</xref>], no specific studies have been conducted to ascertain the disease prevalence in Bulgaria. This form of tuberculosis predominantly afflicts adult patients and is rarely observed in childhood. Clinically, it manifests as slowly progressive monoarthritis of a large joint [<xref ref-type="bibr" rid="B4">4</xref>]. General symptoms are non-specific and include weight loss, subfebrile or febrile temperature, and night sweats [<xref ref-type="bibr" rid="B5">5</xref>]. The joint involvement progresses slowly, characterized by hyperemia and edema. In more advanced stages, patients experience pain and restricted joint mobility. The most commonly affected joints include those of the spine (known as Pott disease), as well as the hip and knee joints [<xref ref-type="bibr" rid="B6">6</xref>]. Historically, in the pre-antibiotic era, the natural course of the disease led to the development of spinal gibbus, severe ankylosis, and permanent functional limitations in the affected joints. However, modern therapeutic approaches have significantly improved outcomes, favorably influencing the disease’s course and facilitating joint function restoration [<xref ref-type="bibr" rid="B7">7</xref>]. Sometimes surgical intervention is deemed necessary.</p>
    </sec>
    <sec sec-type="﻿Conclusion" id="SECID0EWAAC">
      <title>﻿Conclusion</title>
      <p>Despite the reduced frequency of tuberculosis in Bulgaria, it remains a significant concern within childhood pathologies. Advances in laboratory and radiological diagnostic methods have undoubtedly improved our understanding, yet the definitive diagnosis of tuberculosis sometimes unfolds during the course of therapy. Treating pediatric tuberculosis is a complex endeavor that demands a multidisciplinary approach and proceeds deliberately over a period of 6 to 12 months, contingent upon the disease’s specific form.</p>
      <p>The success of this treatment regimen reverberates beyond the individual patient—it profoundly impacts society as a whole. However, amidst the broader landscape of tuberculosis, a rare variants, such as bones and joints tuberculosis, emerges. This form, particularly uncommon in children, warrants special attention. In intricate and challenging cases, early initiation of targeted therapy, and occasionally surgical intervention, significantly influence the disease’s ultimate outcome.</p>
    </sec>
  </body>
  <back>
    <ref-list>
      <title>﻿﻿References</title>
      <ref id="B1">
        <mixed-citation xlink:type="simple">1. Minchev P., Vasileva. P., Kostadinov D., Bogov B., Aleksiev A., Spasova Z., Tsonzorova M., Pramatarov K., Bachyiska E., Velizarova Sv. (2013) Clinical tuberculosis, p. 108-111, p.189-200</mixed-citation>
      </ref>
      <ref id="B2">
        <mixed-citation xlink:type="simple">2. Adrienne Santos-Longhurst, Jill Seladi-Schulman (2019) Types of tuberculosis: <ext-link xlink:href="https://www.healthline.com/health/types-of-tuberculosis" ext-link-type="uri" xlink:type="simple">https://www.healthline.com/health/types-of-tuberculosis</ext-link></mixed-citation>
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