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 <!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.0 20120330//EN" "http://jats.nlm.nih.gov/publishing/1.0/JATS-journalpublishing1.dtd"> <article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" article-type="case-report" dtd-version="1.0" xml:lang="en">
  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">JDRT</journal-id>
      <journal-title-group>
        <journal-title>Journal of Dermatologic Research And Therapy</journal-title>
      </journal-title-group>
      <issn pub-type="epub">2471-2175</issn>
      <publisher>
        <publisher-name>Open Access Pub</publisher-name>
        <publisher-loc>United States</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">JDRT-15-698</article-id>
      <article-id pub-id-type="doi">10.14302/issn.2471-2175.jdrt-15-698</article-id>
      <article-categories>
        <subj-group>
          <subject>case-report</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Bullous Pemphigoid Triggered by Artificial Hip Made of Titanium Alloy: A Case Report and Review of Triggers for Bullous Pemphigoid</article-title>
        <alt-title alt-title-type="running-head">bp triggered by artificial hip.</alt-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Wen-Zhong</surname>
            <given-names>Xiang</given-names>
          </name>
          <xref ref-type="aff" rid="idm1809069836">1</xref>
          <xref ref-type="aff" rid="idm1809070196">*</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Jia</surname>
            <given-names>Deng</given-names>
          </name>
          <xref ref-type="aff" rid="idm1809069836">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ai-E</surname>
            <given-names>Xu</given-names>
          </name>
          <xref ref-type="aff" rid="idm1809069836">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Qi</surname>
            <given-names>Wang</given-names>
          </name>
          <xref ref-type="aff" rid="idm1809069836">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Xiao-Hang</surname>
            <given-names>Du</given-names>
          </name>
          <xref ref-type="aff" rid="idm1809069836">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ping</surname>
            <given-names>Wang</given-names>
          </name>
          <xref ref-type="aff" rid="idm1809069836">1</xref>
        </contrib>
      </contrib-group>
      <aff id="idm1809069836">
        <label>1</label>
        <addr-line>Department of Dermatology, Third Hospital of Hangzhou, Affiliated Hangzhou Clinical College, Anhui Medical University.</addr-line>
      </aff>
      <aff id="idm1809070196">
        <label>*</label>
        <addr-line>Corresponding Author</addr-line>
      </aff>
      <contrib-group>
        <contrib contrib-type="editor">
          <name>
            <surname>Anand</surname>
            <given-names>Rotte</given-names>
          </name>
          <xref ref-type="aff" rid="idm1808911788">1</xref>
        </contrib>
      </contrib-group>
      <aff id="idm1808911788">
        <label>1</label>
        <addr-line>University of British Columbia</addr-line>
      </aff>
      <author-notes>
        <corresp>
    
    Wen-Zhong Xiang, <addr-line>Department of Dermatology, Third Hospital of Hangzhou, Affiliated Hangzhou Clinical College, Anhui Medical University, No. 38 West Lake Avenue, Hangzhou 310009, China.</addr-line> Tel: <phone>86-87808787</phone>, Fax: <fax>+86-57187814481</fax>., Email: <email>xiangwenzhong@126.com</email></corresp>
        <fn fn-type="conflict" id="idm1817120316">
          <p>The authors have declared that no competing interests exist.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub" iso-8601-date="2015-11-25">
        <day>25</day>
        <month>11</month>
        <year>2015</year>
      </pub-date>
      <volume>1</volume>
      <issue>1</issue>
      <fpage>22</fpage>
      <lpage>25</lpage>
      <history>
        <date date-type="received">
          <day>12</day>
          <month>08</month>
          <year>2015</year>
        </date>
        <date date-type="accepted">
          <day>07</day>
          <month>11</month>
          <year>2015</year>
        </date>
        <date date-type="online">
          <day>25</day>
          <month>11</month>
          <year>2015</year>
        </date>
      </history>
      <permissions>
        <copyright-statement>© </copyright-statement>
        <copyright-year>2015</copyright-year>
        <copyright-holder>Wen-Zhong Xiang, et al.</copyright-holder>
        <license 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
        </license>
      </permissions>
      <self-uri xlink:href="http://openaccesspub.org/jdrt/article/199">This article is available from http://openaccesspub.org/jdrt/article/199</self-uri>
      <abstract>
        <p>Bullous pemphigoid (BP) is one of the most common autoimmune blistering diseases. Here, we report an old woman presented with a 2-month history of bullous lesions located just over the skin of the right thigh and buttock where the orthopedics operation was performed using artificial hip made of titanium alloy and a twenty days history of similar lesions involving the rest of the body gradually.</p>
      </abstract>
      <kwd-group>
        <kwd>Erythema</kwd>
        <kwd>artificial hip</kwd>
        <kwd>titanium alloy</kwd>
        <kwd>Bullous pemphigoid</kwd>
      </kwd-group>
      <counts>
        <fig-count count="1"/>
        <table-count count="0"/>
        <page-count count="04"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec id="idm1808915100" sec-type="intro">
      <title>Introduction</title>
      <p>Bullous pemphigoid (BP) is one of the most common autoimmune blistering diseases. Most cases develop in the absence of an identiﬁable trigger, and generally occur in elderly patients <xref ref-type="bibr" rid="ridm1809677572">1</xref>. Although BP is usually idiopathic, some cases induced by chemical and physical triggers as well as medications have been reported <xref ref-type="bibr" rid="ridm1809741596">2</xref><xref ref-type="bibr" rid="ridm1809782196">3</xref>. We report a case of typical BP which was strongly suspected to have been triggered by the artificial hip made of titanium alloy. To our knowledge, this is the first reported case of BP by the artificial hip. Artificial hip should be added to the list of possible triggers for BP and the diagnosis should be considered if blistering develops following hip replacement surgery. </p>
    </sec>
    <sec id="idm1808916540" sec-type="cases">
      <title>Case Report</title>
      <p>We report a 77-year-old woman presented with a 2-month history of bullous lesions located just over the skin of the right thigh and buttock where the orthopedics operation was performed and a twenty days history of similar lesions involving the rest of the body gradually before the patient was referred to our hospital.</p>
      <p>At the beginning of the episodes, she experienced a sudden onset of a femoral neck fracture caused by an accidental fall in May 2011. Then the patient was referred to hospitalization for orthopedics operation at a local hospital. Only seven days after undergoing hip arthroplasty made of titanium alloy, the patient reported severe pruritus and rapid onset of erythema and blistering located just over the skin of the right thigh and buttock where the orthopedics operation was performed. At first presentation, the dermatologist in that hospital diagnosed this patient with contact dermatitis and initiated oral antihistamine, topical application of drug as the main treatment. However, despite the treatment, the patient experienced the recurrent attacks of vesicles, bullae and blood blister for about forty days. More seriously, similar lesions then expanded to the rest of the body gradually for twenty days. </p>
      <p>In July 2011, the patient was admitted to our ward due to recurrent episodes of skin lesions. On physical examination, multiple tense vesicles, bullae and blood blister were seen over the extremities and trunk with a background of erythema (<xref ref-type="fig" rid="idm1809066692">Figure 1</xref>A and B). In addition, Nikolskiy’s sign was negative. A clinical diagnosis of BP was considered based on the clinical manifestation. The right hip prosthesis made of titanium alloy can be seen by the computed tomography scanning <xref ref-type="fig" rid="idm1809066692">Figure 1</xref>C). The patient had a history of penicillin allergy, 17-year-history of hypertension and no personal history or family history of BP. She took metoprolol succinate sustained-release tablets to lower blood pressure for more than 8 years. The biopsy specimen taken from a recently developed intact vesicle on the patient’s left arm shows a subepidermal blister, filled with an inflammatory cell infiltration consisting of numerous eosinophils, neutrophils, and a small number of lymphocytes (<xref ref-type="fig" rid="idm1809066692">Figure 1</xref>D). Direct immunoﬂuorescence showed IgG and C3 at the dermo-epidermal junction. Moreover, we detected the presence of circulating antibodies against BP180 in this patient . All the clinical manifestations and laboratory examinations conﬁrmed the final diagnoses of BP. The patient was treated with high-dose intravenous methylprednisolone (60mg once daily for one week) and intravenous immunoglobulin (IVIG, 0.4g/kg/d for 5d). Then oral prednisone 50 mg daily was continued and the lesions had completely resolved within 5 weeks. </p>
      <fig id="idm1809066692">
        <label>Figure 1.</label>
        <caption>
          <title> (A) Erythema and blisters on the skin of the right thigh. (B) Multiple tense vesicles, bullae and blood blister on the legs on a background of erythema. (C) The right hip prosthesis made of titanium alloy can be seen by the computed tomography scanning.  (D) Histopathology revealed a subepidermal blister (haematoxylin and eosin staining, original magnification x 100).</title>
        </caption>
        <graphic xlink:href="images/image1.jpg" mime-subtype="jpg"/>
      </fig>
    </sec>
    <sec id="idm1808913948" sec-type="discussion">
      <title>Discussion</title>
      <p>BP is one of the most common autoimmune blistering diseases. Many factors may be responsible for the onset of BP including drug intake, physical agents, and viral infections <xref ref-type="bibr" rid="ridm1809539116">4</xref>. Medications are the most common cause of development for BP. Both systemic and topical drugs have been reported to be triggers in the development of BP such as iodine and etanercept <xref ref-type="bibr" rid="ridm1809677572">1</xref>, dipeptidyl peptidase-IV inhibitors plus metformin <xref ref-type="bibr" rid="ridm1809536236">5</xref>, loop diuretics <xref ref-type="bibr" rid="ridm1809531500">6</xref>, ophthalmic preparations <xref ref-type="bibr" rid="ridm1809527036">7</xref>. In addition, thermal burns <xref ref-type="bibr" rid="ridm1809518084">8</xref><xref ref-type="bibr" rid="ridm1809516500">9</xref><xref ref-type="bibr" rid="ridm1809520892">10</xref><xref ref-type="bibr" rid="ridm1809501412">11</xref><xref ref-type="bibr" rid="ridm1809498532">12</xref><xref ref-type="bibr" rid="ridm1809492484">13</xref> and boiling water burn <xref ref-type="bibr" rid="ridm1809741596">2</xref> can induce BP. Scabies cannot be ruled out of the list of probabilities, scabies infestation triggering bullous pemphigoid should be distinguished from bullous pemphigoid-like scabies<xref ref-type="bibr" rid="ridm1809506668">14</xref>. However it is still not clear about the mechanism responsible for the eruption and exacerbation of BP in the cases mentioned above. </p>
      <p>To our knowledge, this is the first reported case of BP by the artificial hip made of titanium alloy. The reasons for the onset of bullous pemphigoid triggered by titanium alloy hip remain unknown but may be related to cytotoxicity of some titanium alloys containing molybdenum, niobium, and silicon <xref ref-type="bibr" rid="ridm1809463652">15</xref>. Artificial hip should be added to the list of possible triggers for BP and the diagnosis should be considered if blistering develops following hip replacement surgery.</p>
    </sec>
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