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    Carlos Hernández
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    The document contains the title "Retrograde urethrogram with moderate stricture" and various HTML elements related to displaying an image, including div tags containing text like the copyright and links to print or email the image.

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    The document contains the title "Retrograde urethrogram with moderate stricture" and various HTML elements related to displaying an image, including div tags containing text like the copyright and links to print or email the image.

    Copyright:

    © All Rights Reserved
    Download as TXT, PDF, TXT or read online from Scribd
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    821 views225 pages

    18

    Uploaded by

    Carlos Hernández
    The document contains the title "Retrograde urethrogram with moderate stricture" and various HTML elements related to displaying an image, including div tags containing text like the copyright and links to print or email the image.

    Copyright:

    © All Rights Reserved
    Download as TXT, PDF, TXT or read online from Scribd
    Flag for inappropriate content
    of 225

    var title_f0_18_288="Retrograde urethrogram with moderate stricture";

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    " </div>",
    " <div class=\"lgnd\">",
    " Active shoulder abduction exercises are used to strengthen the supraspinatus
    muscle prior to the addition of resistance.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " Courtesy of Craig Parsons, MS, PT and the Physical Therapy Network.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
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    var title_f0_18_290="AIDS related KS skin";
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    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
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    " </div>",
    " <div class=\"lgnd\">",
    " Skin lesions in a patient with AIDS-related Kaposi's sarcoma who presented
    with simultaneous cutaneous and gastrointestinal disease.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " By permission from van den Brink, MR, Dezube, BJ, J Clin Oncol 1997;
    15:1283.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
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    " </div>",
    " <div class=\"lgnd\">",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " Audio file courtesy of Dr. Massimo Imazio; Figure reproduced with permission
    from: Bickley LS, Szilagyi P. Bates' Guide to Physical Examination and History
    Taking, 8th Ed, Lippincott Williams &amp; Wilkins, Philadelphia 2003. Copyright
    &copy; 2003 Lippincott Williams &amp; Wilkins.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
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    var outline_f0_18_291=null;
    var title_f0_18_292="Microcystic adnexal carcinoma on cheek";
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    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
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    title=\"Print this page\"/>",
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    " <a class=\"icontxt textLink\" href=\"?imageKey=DERM
    %2F86194&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\"
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    " Print",
    " </a>",
    " <a class=\"etacLink\" href=\"#\">",
    " <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
    title=\"Email graphic(s)\"/>",
    " </a>",
    " <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
    " Email",
    " </a>",
    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\" style=\"width: 470px\">",
    " <div class=\"ttl\">",
    " Microcystic adnexal carcinoma",
    " </div>",
    " <div class=\"cntnt\" style=\"width: 447px; height: 504px; background-image:
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    1NVbmRjIm9cAnseKiZivLHcR0pjTCaRV6DFO76gtGabDagYEEdxUKSBJC235fQUzzDGu3OVqAyENuAIDU2x
    Jlmd0ILKG57ZqHeCQMHj9KN6sp2k5pkcwWULIFzjjPelYpSJt0u35cketKkjRtyGwaieQDoBt9Ka90pT5jy
    DwKbVgvcsySCRiXUYx3qiHHnlByOophukznqe5qGG4Lu3lqSWNIQs8J83dG3J4welUJRKr7T174rSl3LguO
    RWZdOBISD9arcUZM89UAjNO+lFFeiziRKORR0+lFFIYjHjgcUzHfFFFOw0LmnFNwoopDImDL16U1hnvRRQ0
    NDO/tQP0oopDsL3qWJzGwIoopMFozb0+7DY+bFa6Shsc0UVzz0djQnR0IyG7cgVVu49/I5IooqExoitZ2UY
    3EYrVhuy0eCRmiihlyRHefNES2Mmsjc0Em5c7aKKaY4o0oL3dgZxV2KRp22ocD1NFFR1BqyuWjaiNTxkkda
    yLg7GYKeh6UUVVyaeu5NaSMrBgQa27e5HXkHvRRWbepbimSmYs+2MEsfWoXTD4PLdz3ooqW9CUrFuEsAB1H
    0rPvAUn6naaKKfQcdxA+3Bz0oe7M0gRMbR1ooouNrqWVm2njg+lYd4TLehR06miihMUEaCJvjA43DpirFsR
    ET5md/vRRTuK2tiN5RJJwasx3DohUYCN196KKFJpilG5lagsbSEoSH71DGGjYeYSc96KKq99S1sXknGQCRz
    UiSkcDBz60UVF7gTB3PytyOxqteOFcFOCKKKd9BJajFvDncc8VYF2HX5yDRRSvYbihEnQPnp+NR3cyM2Rg4
    5ooqkybalZ7sKhwcGmRy5+
    +27PpRRTZY2WYIMRrx3NTwyFI0KkZPXFFFIlq4lzckDJ5zWVPKCefvZyaKKuJm0f/Z);\">",
    " </div>",
    " <div class=\"lgnd\">",
    " Microcystic adnexal carcinoma presenting as a white-yellow plaque on the
    cheek.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_18_292=[""].join("\n");
    var outline_f0_18_292=null;
    var title_f0_18_293="Tetanus immune globulin (human): Drug information";
    var content_f0_18_293=[" <noscript>",
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    " <!-- TC:TOPIC_PAGE -->",
    " <div id=\"topicContent\">",
    " <div id=\"drugTitle\">",
    " Tetanus immune globulin (human): Drug information",
    " </div>",
    " <div id=\"lexiTitleImg\">",
    " <img height=\"17\" src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\"
    width=\"71\"/>",
    " </div>",
    " <div class=\"clear\">",
    " </div>",
    " <div id=\"drugCopy\">",
    " Copyright 1978-2013 Lexicomp, Inc. All rights reserved.",
    " </div>",
    " <div id=\"topicText\">",
    " (For additional information",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?11/18/11555?source=see_link\">",
    " see \"Tetanus immune globulin (human): Patient drug information\"",
    " </a>",
    " and",
    " <a class=\"drug drug_pediatric\" href=\"UTD.htm?39/46/40676?
    source=see_link\">",
    " see \"Tetanus immune globulin (human): Pediatric drug information\"",
    " </a>",
    " )",
    " <br/>",
    " For abbreviations and symbols that may be used in Lexicomp (",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?23/39/24183\">",
    " show table",
    " </a>",
    " )",
    " <div class=\"list ubnlist drugH1Div drugBrandNames\" id=\"F226065\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Brand Names: U.S.",
    " </span>",
    " <ul>",
    " <li>",
    " HyperTET&trade; S/D",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"list cbnlist drugH1Div drugBrandNames\" id=\"F226066\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Brand Names: Canada",
    " </span>",
    " <ul>",
    " <li>",
    " HyperTET&trade; S/D",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"ex_sect_xr thclist drugH1Div drugBrandNames\" id=\"F226076\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pharmacologic Category",
    " </span>",
    " <ul>",
    " <li>",
    " Immune Globulin",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"block doa drugH1Div\" id=\"F226067\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Adult",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Prophylaxis of tetanus:",
    " </b>",
    " I.M.: 250 units",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Tetanus prophylaxis in wound management:",
    " </b>",
    " I.M.: Tetanus prophylaxis in patients with wounds should consider if the
    wound is clean or contaminated, the immunization status of the patient, proper use
    of tetanus toxoid and/or tetanus immune globulin (TIG), wound cleaning, and (if
    required) surgical debridement and the proper use of antibiotics. Patients with an
    uncertain or incomplete tetanus immunization status should have additional follow
    up to ensure a series is completed. Patients with a history of Arthus reaction
    following a previous dose of a tetanus toxoid-containing vaccine should not receive
    a tetanus toxoid-containing vaccine until &gt;10 years after the most recent dose
    even if they have a wound that is neither clean nor minor. See table.",
    " </p>",
    " <table border=\"1\" frame=\"border\" rules=\"all\">",
    " <caption style=\"text-align:center;\">",
    " Tetanus Prophylaxis in Wound Management",
    " </caption>",
    " <col align=\"center\" width=\"145\">",
    " </col>",
    " <col align=\"center\" width=\"85\">",
    " </col>",
    " <col align=\"center\" width=\"85\">",
    " </col>",
    " <col align=\"center\" width=\"85\">",
    " </col>",
    " <col align=\"center\" width=\"85\">",
    " </col>",
    " <thead valign=\"middle\">",
    " <tr>",
    " <th align=\"center\" rowspan=\"2\" valign=\"middle\">",
    " <p style=\"text-indent:0em;\">",
    " History of Tetanus Immunization Doses",
    " </p>",
    " </th>",
    " <th align=\"center\" colspan=\"2\">",
    " <p style=\"text-indent:0em;\">",
    " Clean, Minor Wounds",
    " </p>",
    " </th>",
    " <th align=\"center\" colspan=\"2\">",
    " <p style=\"text-indent:0em;\">",
    " All Other Wounds",
    " <sup>",
    " 1",
    " </sup>",
    " </p>",
    " </th>",
    " </tr>",
    " <tr>",
    " <th align=\"center\">",
    " <p style=\"text-indent:0em;\">",
    " Tetanus Toxoid",
    " <sup>",
    " 2",
    " </sup>",
    " </p>",
    " </th>",
    " <th align=\"center\">",
    " <p style=\"text-indent:0em;\">",
    " TIG",
    " </p>",
    " </th>",
    " <th align=\"center\">",
    " <p style=\"text-indent:0em;\">",
    " Tetanus Toxoid",
    " <sup>",
    " 2",
    " </sup>",
    " </p>",
    " </th>",
    " <th align=\"center\">",
    " <p style=\"text-indent:0em;\">",
    " TIG",
    " </p>",
    " </th>",
    " </tr>",
    " </thead>",
    " <tfoot valign=\"middle\">",
    " <tr>",
    " <td align=\"left\" colspan=\"5\">",
    " <p style=\"text-indent:0em;\">",
    " <sup>",
    " 1",
    " </sup>",
    " Such as, but not limited to, wounds contaminated with dirt, feces, soil,
    and saliva; puncture wounds; wounds from crushing, tears, burns, and frostbite.",
    " </p>",
    " </td>",
    " </tr>",
    " <tr>",
    " <td align=\"left\" colspan=\"5\">",
    " <p style=\"text-indent:0em;\">",
    " <sup>",
    " 2",
    " </sup>",
    " Tetanus toxoid in this chart refers to a tetanus toxoid-containing
    vaccine. For children &lt;7 years of age, DTaP (DT, if pertussis vaccine
    contraindicated) is preferred to tetanus toxoid alone. For children &ge;7 years and
    Adults, Td preferred to tetanus toxoid alone; Tdap may be preferred if the patient
    has not previously been vaccinated with Tdap.",
    " </p>",
    " </td>",
    " </tr>",
    " <tr>",
    " <td align=\"left\" colspan=\"5\">",
    " <p style=\"text-indent:0em;\">",
    " <sup>",
    " 3",
    " </sup>",
    " Yes, if &ge;10 years since last dose.",
    " </p>",
    " </td>",
    " </tr>",
    " <tr>",
    " <td align=\"left\" colspan=\"5\">",
    " <p style=\"text-indent:0em;\">",
    " <sup>",
    " 4",
    " </sup>",
    " Yes, if &ge;5 years since last dose.",
    " </p>",
    " </td>",
    " </tr>",
    " <tr>",
    " <td align=\"left\" colspan=\"5\">",
    " <p style=\"text-indent:0em;\">",
    " Adapted from CDC \"Yellow Book\" (",
    " <i>",
    " Health Information for International Travel 2010",
    " </i>",
    " ), \"Routine Vaccine-Preventable Diseases, Tetanus\" (available at",
    " <a href=\"file://www.cdc.gov/yellowbook\" target=\"_blank\">",
    " file://www.cdc.gov/yellowbook",
    " </a>",
    " ) and",
    " <i>",
    " MMWR",
    " </i>",
    " 2006, 55(RR-17).",
    " </p>",
    " </td>",
    " </tr>",
    " <tr>",
    " <td align=\"left\" colspan=\"5\" valign=\"top\">",
    " <p style=\"text-indent:0em;\">",
    " Abbreviations:",
    " <b>",
    " DT",
    " </b>",
    " = Diphtheria and Tetanus Toxoids (formulation for age &le;6 years);",
    " <b>",
    " DTaP",
    " </b>",
    " = Diphtheria and Tetanus Toxoids, and Acellular Pertussis (formulation
    for age &le;6 years; Daptacel&reg;, Infanrix&reg;);",
    " <b>",
    " Td",
    " </b>",
    " = Diphtheria and Tetanus Toxoids (formulation for age &ge;7 years;
    Decavac&reg;,Tenivac&trade;);",
    " <b>",
    " TT",
    " </b>",
    " = Tetanus toxoid (adsorbed [formulation for age &ge;7 years]);",
    " <b>",
    " Tdap",
    " </b>",
    " = Diphtheria and Tetanus Toxoids, and Acellular Pertussis (Adacel&reg; or
    Boostrix&reg; [formulations for age &ge;7 years]);",
    " <b>",
    " TIG",
    " </b>",
    " = Tetanus Immune Globulin",
    " </p>",
    " </td>",
    " </tr>",
    " </tfoot>",
    " <tbody valign=\"middle\">",
    " <tr>",
    " <td align=\"center\">",
    " <p style=\"text-indent:0em;\">",
    " <b>",
    " Uncertain or &lt;3 doses",
    " </b>",
    " </p>",
    " </td>",
    " <td align=\"center\">",
    " <p style=\"text-indent:0em;\">",
    " Yes",
    " </p>",
    " </td>",
    " <td align=\"center\">",
    " <p style=\"text-indent:0em;\">",
    " No",
    " </p>",
    " </td>",
    " <td align=\"center\">",
    " <p style=\"text-indent:0em;\">",
    " Yes",
    " </p>",
    " </td>",
    " <td align=\"center\">",
    " <p style=\"text-indent:0em;\">",
    " Yes",
    " </p>",
    " </td>",
    " </tr>",
    " <tr>",
    " <td align=\"center\">",
    " <p style=\"text-indent:0em;\">",
    " <b>",
    " 3 or more doses",
    " </b>",
    " </p>",
    " </td>",
    " <td align=\"center\">",
    " <p style=\"text-indent:0em;\">",
    " No",
    " <sup>",
    " 3",
    " </sup>",
    " </p>",
    " </td>",
    " <td align=\"center\">",
    " <p style=\"text-indent:0em;\">",
    " No",
    " </p>",
    " </td>",
    " <td align=\"center\">",
    " <p style=\"text-indent:0em;\">",
    " No",
    " <sup>",
    " 4",
    " </sup>",
    " </p>",
    " </td>",
    " <td align=\"center\">",
    " <p style=\"text-indent:0em;\">",
    " No",
    " </p>",
    " </td>",
    " </tr>",
    " </tbody>",
    " </table>",
    " <p style=\"text-indent:-2em;margin-left:2em;margin-top:2em;text-
    align:justify;\">",
    " <b>",
    " Treatment of tetanus:",
    " </b>",
    " I.M.: 500-6000 units. Infiltration of part of the dose around the wound is
    recommended.",
    " </p>",
    " </div>",
    " <div class=\"block dop drugH1Div\" id=\"F226072\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Pediatric",
    " </span>",
    " <p>",
    " (For additional information",
    " <a class=\"drug drug_pediatric\" href=\"UTD.htm?39/46/40676?
    source=see_link\">",
    " see \"Tetanus immune globulin (human): Pediatric drug information\"",
    " </a>",
    " )",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Prophylaxis of tetanus:",
    " </b>",
    " I.M.:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Children &lt;7 years: 4 units/kg; some recommend administering 250 units to
    small children",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Children &ge;7 years: Refer to adult dosing.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Tetanus prophylaxis in wound management:",
    " </b>",
    " Refer to adult dosing.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Treatment of tetanus:",
    " </b>",
    " Refer to adult dosing.",
    " </p>",
    " </div>",
    " <div class=\"block doe drugH1Div\" id=\"F226068\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Geriatric",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Refer to adult dosing.",
    " </p>",
    " </div>",
    " <div class=\"block foc drugH1Div\" id=\"F226053\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosage Forms: U.S.",
    " </span>",
    " <p style=\"text-indent:0em;text-align:justify;display:inline\">",
    " Excipient information presented when available (limited, particularly for
    generics); consult specific product labeling.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Injection, solution [preservative free]:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " HyperTET&trade; S/D: 250 units/mL (~1 mL)",
    " </p>",
    " </div>",
    " <div class=\"block geq drugH1Div\" id=\"F226040\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Generic Equivalent Available: U.S.",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " No",
    " </p>",
    " </div>",
    " <div class=\"block adm drugH1Div\" id=\"F226056\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Administration",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Do not administer I.V.; I.M. use only. Administer in the anterolateral
    aspects of the upper thigh or the deltoid muscle of the upper arm. Avoid gluteal
    region due to risk of injury to sciatic nerve; if gluteal region is used,
    administer only in the upper outer quadrant. If tetanus vaccine and tetanus immune
    globulin are administered simultaneously, separate sites should be used for each
    injection. When used for the treatment of tetanus, infiltration of part of the dose
    around the wound is recommended.",
    " </p>",
    " </div>",
    " <div class=\"block use drugH1Div\" id=\"F226054\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Use",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Prophylaxis against tetanus following injury in patients where immunization
    status is not known or uncertain",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " The Advisory Committee on Immunization Practices (ACIP) recommends passive
    immunization with TIG for the following:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " &bull; Persons with a wound that is not clean or minor and in whom
    contraindications to a tetanus-toxoid containing vaccine exist and they have not
    completed a primary series of tetanus toxoid immunization.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " &bull; Persons who are wounded in bombings or similar mass casualty events
    who have penetrating injuries or nonintact skin exposure and who cannot confirm
    receipt of a tetanus booster within the previous 5 years. In case of shortage, use
    should be reserved for persons &ge;60 years of age.",
    " </p>",
    " </div>",
    " <div class=\"block ars drugH1Div\" id=\"F226074\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Adverse Reactions Significant",
    " </span>",
    " <p style=\"text-indent:0em;text-align:justify;display:inline\">",
    " Frequency not defined.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Central nervous system: Temperature increased",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Dermatologic: Angioneurotic edema (rare)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Local: Injection site: Pain, soreness, tenderness",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Renal: Nephritic syndrome (rare)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Miscellaneous: Anaphylactic shock (rare)",
    " </p>",
    " </div>",
    " <div class=\"block war drugH1Div\" id=\"F226044\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Warnings/Precautions",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " <i>",
    " Concerns related to adverse effects:",
    " </i>",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Anaphylaxis/hypersensitivity reactions: Hypersensitivity and
    anaphylactic reactions can occur; immediate treatment (including epinephrine
    1:1000) should be available. Use with caution in patients with isolated
    immunoglobulin A deficiency or a history of systemic hypersensitivity to human
    immunoglobulins.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " <i>",
    " Disease-related concerns:",
    " </i>",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Bleeding disorders: Use with caution in patients with thrombocytopenia
    or coagulation disorders; I.M. injections may be contraindicated.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " <i>",
    " Dosage form specific issues:",
    " </i>",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Human plasma: Product of human plasma; may potentially contain
    infectious agents which could transmit disease. Screening of donors, as well as
    testing and/or inactivation or removal of certain viruses, reduces the risk.
    Infections thought to be transmitted by this product should be reported to the
    manufacturer.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " <i>",
    " Other warnings/precautions:",
    " </i>",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Administration: Not for intravenous administration.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Skin testing: Skin testing should not be performed as local irritation
    can occur and be misinterpreted as a positive reaction.",
    " </p>",
    " </div>",
    " <div class=\"block cyt drugH1Div\" id=\"F13300119\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Metabolism/Transport Effects",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " None known.",
    " </p>",
    " </div>",
    " <div class=\"block dri drugH1Div\" id=\"F226048\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Drug Interactions",
    " </span>",
    " <br/>",
    " <br/>",
    " <div class=\"lexi\" id=\"lexiInteractAddInfo\">",
    " (For additional information:",
    " <a class=\"dip\" href=\"./drug-interaction\" target=\"_blank\">",
    " Launch Lexi-Interact&trade; Drug Interactions Program",
    " </a>",
    " )",
    " </div>",
    " <div class=\"lexi\" id=\"lexiInteractImgB\">",
    " <img border=\"0\" height=\"17\"
    src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\" width=\"71\"/>",
    " </div>",
    " <div class=\"clear\">",
    " </div>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Vaccines (Live): Immune Globulins may diminish the therapeutic effect of
    Vaccines (Live). Management: Live organism vaccination should be withheld for up
    to 6 months following immune globulin administration. Live vaccine given
    immediately prior to immune globulin may require repeat vaccination.",
    " <b>",
    " Exceptions:",
    " </b>",
    " Yellow Fever Vaccine.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " </div>",
    " <div class=\"block prf drugH1Div\" id=\"F226050\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pregnancy Risk Factor",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " C (",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?16/42/17068\">",
    " show table",
    " </a>",
    " )",
    " </p>",
    " </div>",
    " <div class=\"block pri drugH1Div\" id=\"F6742397\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pregnancy Implications",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Animal reproduction studies have not been conducted. Tetanus immune globulin
    and a tetanus toxoid containing vaccine are recommended by the ACIP as part of the
    standard wound management to prevent tetanus in pregnant women.",
    " </p>",
    " </div>",
    " <div class=\"block fee drugH1Div\" id=\"F16323952\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pricing: U.S. (Medi-Span&reg;)",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Injection",
    " </b>",
    " (HyperTET S/D Intramuscular)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " 250 units/mL (1): $411.94",
    " </p>",
    " </div>",
    " <div class=\"list fbnlist drugH1Div drugBrandNames\" id=\"F226061\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " International Brand Names",
    " </span>",
    " <ul>",
    " <li>",
    " BayTet (MX, PK);",
    " </li>",
    " <li>",
    " Clostet (PH);",
    " </li>",
    " <li>",
    " Hyper-Tet (HK, KP);",
    " </li>",
    " <li>",
    " Hypertet (IL, TW);",
    " </li>",
    " <li>",
    " Igantet (SG);",
    " </li>",
    " <li>",
    " Ronsen Yipu (CL);",
    " </li>",
    " <li>",
    " Sero-Tet (MY, PH);",
    " </li>",
    " <li>",
    " Tetabulin (AT, CZ, IT, PL);",
    " </li>",
    " <li>",
    " Tetabuline (BE);",
    " </li>",
    " <li>",
    " Tetagam (HK, ID, ZA);",
    " </li>",
    " <li>",
    " Tetagam N (CH, DE);",
    " </li>",
    " <li>",
    " Tetagam-P (GR, TH);",
    " </li>",
    " <li>",
    " Tetaglobulin (DE, IN);",
    " </li>",
    " <li>",
    " Tetaglobuline (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, MY,
    NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW);",
    " </li>",
    " <li>",
    " Tetanobulin (TW);",
    " </li>",
    " <li>",
    " Tetanobulin S/D (DE);",
    " </li>",
    " <li>",
    " Tetanogamma (DO);",
    " </li>",
    " <li>",
    " Tetanogamma P (MX);",
    " </li>",
    " <li>",
    " Tetuman (NL);",
    " </li>",
    " <li>",
    " Tetuman berna (HK, MY, PE, TH, TW)",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"block pha drugH1Div\" id=\"F226043\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Mechanism of Action",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Passive immunity toward tetanus",
    " </p>",
    " </div>",
    " <div class=\"block phk drugH1Div\" id=\"F226058\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pharmacodynamics/Kinetics",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Absorption: Well absorbed",
    " </p>",
    " </div>",
    " </div>",
    " <div id=\"topicAgreement\">",
    " Use of UpToDate is subject to the",
    " <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
    target=\"_blank\">",
    " Subscription and License Agreement",
    " </a>",
    " .",
    " </div>",
    " <div class=\"headingAnchor\" id=\"references\">",
    " <h1>",
    " REFERENCES",
    " </h1>",
    " <ol id=\"reference\">",
    " <li>",
    " <div class=\"reference\">",
    " Centers for Disease Control, &ldquo;Diphtheria, Tetanus, and Pertussis:
    Recommendations for Vaccine Use and Other Preventive Measures,&rdquo;",
    " <i>",
    " MMWR Recomm Rep",
    " </i>",
    " , 1991, 40(RR-10):1-28",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?0/18/293/abstract-text/1865873/pubmed\" id=\"1865873\"
    target=\"_blank\">",
    " 1865873",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Centers for Disease Control, &ldquo;Prevention of Pertussis, Tetanus, and
    Diphtheria Among Pregnant and Postpartum Women and Their Infants, Recommendations
    of the Advisory Committee on Immunization Practices (ACIP),&rdquo;",
    " <i>",
    " MMWR Recomm Rep",
    " </i>",
    " , 2008, 57(early release):1-47. Available at",
    " <a href=\"file://www.cdc.gov/mmwr/preview/mmwrhtml/rr57e0514a1.htm?
    s_cid=rr57e0514a1_e%20\" target=\"_blank\">",
    " file://www.cdc.gov/mmwr/preview/mmwrhtml/rr57e0514a1.htm?
    s_cid=rr57e0514a1_e",
    " </a>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Centers for Disease Control, &ldquo;Recommendations for Postexposure
    Interventions to Prevent Infection With Hepatitis B Virus, Hepatitis C Virus, or
    Human Immunodeficiency Virus, and Tetanus in Persons Wounded During Bombings and
    Other Mass-Casualty Events -- United States, 2008: Recommendations of the Centers
    For Disease Control And Prevention (CDC),&rdquo;",
    " <i>",
    " MMWR Recomm Rep",
    " </i>",
    " , 2008, 57(RR-6):1-21.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?0/18/293/abstract-text/18668022/pubmed\" id=\"18668022\"
    target=\"_blank\">",
    " 18668022",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Cohen V, Jellinek SP, Teperikidis L, et al, &ldquo;Room-Temperature Storage
    of Medications Labeled for Refrigeration,&rdquo;",
    " <i>",
    " Am J Health-Syst Pharm",
    " </i>",
    " , 2007, 64(16):1711-15.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?0/18/293/abstract-text/17687059/pubmed\" id=\"17687059\"
    target=\"_blank\">",
    " 17687059",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " </ol>",
    " </div>",
    " <div id=\"topicVersionRevision\">",
    " Topic 9983 Version 30.0",
    " </div>",
    " </div>",
    " <div id=\"footer\">",
    " <div id=\"supportFooter\">",
    " <span class=\"sfInfo\">",
    " &copy; 2013 UpToDate, Inc. All rights reserved.",
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    " |",
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    " <a class=\"licenseLink\" href=\"./license\" id=\"sla_footer\">",
    " Subscription and License Agreement",
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    " Release: 21.6- C21.56",
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    " <br/>",
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    " Licensed to:",
    " <span class=\"emphasis\">",
    " AsanBook Dig. Med. Lib.",
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    " Support Tag: [0505-197.136.42.3-97C5FA2E12-S244013.14]",
    " <br/>",
    " </span>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_18_293=[""].join("\n");
    var outline_f0_18_293=[" <div id=\"toggleOutline\">",
    " <a href=\"#\" title=\"Collapse Topic Outline\">",
    " <img alt=\"\" src=\"./../images/orange_arrow_left.myextg\"/>",
    " </a>",
    " </div>",
    " <div id=\"innerOutline\">",
    " <h1>",
    " TOPIC OUTLINE",
    " </h1>",
    " <div id=\"outline\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F226065\">",
    " Brand Names: U.S.",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F226066\">",
    " Brand Names: Canada",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F226076\">",
    " Pharmacologic Category",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F226067\">",
    " Dosing: Adult",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F226072\">",
    " Dosing: Pediatric",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F226068\">",
    " Dosing: Geriatric",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F226053\">",
    " Dosage Forms: U.S.",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F226040\">",
    " Generic Equivalent Available: U.S.",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F226056\">",
    " Administration",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F226054\">",
    " Use",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F226074\">",
    " Adverse Reactions Significant",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F226044\">",
    " Warnings/Precautions",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F13300119\">",
    " Metabolism/Transport Effects",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F226048\">",
    " Drug Interactions",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F226050\">",
    " Pregnancy Risk Factor",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F6742397\">",
    " Pregnancy Implications",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F16323952\">",
    " Pricing: U.S. (Medi-Span&reg;)",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F226061\">",
    " International Brand Names",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F226043\">",
    " Mechanism of Action",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F226058\">",
    " Pharmacodynamics/Kinetics",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " <div class=\"openRelatedGraphics\" id=\"DRUG_GEN/9983\" rel=\"outline_link\">",
    " GRAPHICS",
    " <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
    " View All",
    " </a>",
    " </div>",
    " </h1>",
    " <div id=\"relatedGraphics\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <div class=\"openRelatedGraphics\" id=\"DRUG_GEN/9983|TAB\">",
    " <a href=\"#\" title=\"TABLES\">",
    " TABLES",
    " </a>",
    " </div>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?23/39/24183\"
    title=\"Lexicomp clinical abbreviations\">",
    " Lexicomp clinical abbreviations",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " RELATED TOPICS",
    " </h1>",
    " <div id=\"relatedTopics\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?11/18/11555?
    source=related_link\">",
    " Tetanus immune globulin (human): Patient drug information",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_pediatric\" href=\"UTD.htm?39/46/40676?
    source=related_link\">",
    " Tetanus immune globulin (human): Pediatric drug information",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " </div>"].join("\n");
    var title_f0_18_294="Anakinra: Drug information";
    var content_f0_18_294=[" <noscript>",
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    " <!-- TC:TOPIC_PAGE -->",
    " <div id=\"topicContent\">",
    " <div id=\"drugTitle\">",
    " Anakinra: Drug information",
    " </div>",
    " <div id=\"lexiTitleImg\">",
    " <img height=\"17\" src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\"
    width=\"71\"/>",
    " </div>",
    " <div class=\"clear\">",
    " </div>",
    " <div id=\"drugCopy\">",
    " Copyright 1978-2013 Lexicomp, Inc. All rights reserved.",
    " </div>",
    " <div id=\"topicText\">",
    " (For additional information",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?0/10/163?source=see_link\">",
    " see \"Anakinra: Patient drug information\"",
    " </a>",
    " and",
    " <a class=\"drug drug_pediatric\" href=\"UTD.htm?32/52/33605?
    source=see_link\">",
    " see \"Anakinra: Pediatric drug information\"",
    " </a>",
    " )",
    " <br/>",
    " For abbreviations and symbols that may be used in Lexicomp (",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?23/39/24183\">",
    " show table",
    " </a>",
    " )",
    " <div class=\"list ubnlist drugH1Div drugBrandNames\" id=\"F135465\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Brand Names: U.S.",
    " </span>",
    " <ul>",
    " <li>",
    " Kineret&reg;",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"list cbnlist drugH1Div drugBrandNames\" id=\"F135466\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Brand Names: Canada",
    " </span>",
    " <ul>",
    " <li>",
    " Kineret&reg;",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"ex_sect_xr thclist drugH1Div drugBrandNames\" id=\"F135484\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pharmacologic Category",
    " </span>",
    " <ul>",
    " <li>",
    " Antirheumatic, Disease Modifying;",
    " </li>",
    " <li>",
    " Interleukin-1 Receptor Antagonist",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"block doa drugH1Div\" id=\"F135468\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Adult",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " <b>",
    " Neonatal-onset multisystem inflammatory disease (NOMID):",
    " </b>",
    " SubQ: Initial: 1-2 mg/kg daily in 1-2 divided doses; adjust dose in 0.5-1
    mg/kg increments as needed; usual maintenance dose: 3-4 mg/kg daily (maximum: 8
    mg/kg daily).",
    " <b>",
    " Note:",
    " </b>",
    " The prefilled syringe does not allow doses lower than 20 mg to be
    administered.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " <b>",
    " Rheumatoid arthritis (RA):",
    " </b>",
    " SubQ: 100 mg once daily (administer at approximately the same time each
    day)",
    " </p>",
    " </div>",
    " <div class=\"block dop drugH1Div\" id=\"F16330957\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Pediatric",
    " </span>",
    " <p>",
    " (For additional information",
    " <a class=\"drug drug_pediatric\" href=\"UTD.htm?32/52/33605?
    source=see_link\">",
    " see \"Anakinra: Pediatric drug information\"",
    " </a>",
    " )",
    " </p>",
    " <p style=\"text-indent:0em;display:inline\">",
    " <b>",
    " Neonatal-onset multisystem inflammatory disease (NOMID):",
    " </b>",
    " Infants, Children, and Adolescents: SubQ: Refer to adult dosing.",
    " </p>",
    " </div>",
    " <div class=\"block doe drugH1Div\" id=\"F135469\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Geriatric",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Refer to adult dosing.",
    " </p>",
    " </div>",
    " <div class=\"block dor drugH1Div\" id=\"F135470\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Renal Impairment",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;margin-top:0em;text-
    align:justify;\">",
    " Cl",
    " <sub>",
    " cr",
    " </sub>",
    " &ge;30 mL/minute: No dosage adjustment necessary.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;margin-top:0em;text-
    align:justify;\">",
    " Cl",
    " <sub>",
    " cr",
    " </sub>",
    " &lt;30 mL/minute:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;margin-top:0em;text-
    align:justify;\">",
    " NOMID: Infants, Children, Adolescents, and Adults: No dosage adjustment
    necessary; however, decrease frequency of administration to every other day.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;margin-top:0em;text-
    align:justify;\">",
    " RA: Adults: 100 mg every other day",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;margin-top:0em;text-
    align:justify;\">",
    " ESRD (",
    " <b>",
    " Note:",
    " </b>",
    " &lt;2.5% of the dose is removed by hemodialysis or CAPD):",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;margin-top:0em;text-
    align:justify;\">",
    " NOMID: Infants, Children, Adolescents, and Adults: No dosage adjustment
    necessary; however, decrease frequency of administration to every other day.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;margin-top:0em;text-
    align:justify;\">",
    " RA: Adults: 100 mg every other day",
    " </p>",
    " </div>",
    " <div class=\"block doh drugH1Div\" id=\"F13258473\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Hepatic Impairment",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " No dosage adjustments provided in the manufacturer&rsquo;s labeling (has not
    been studied).",
    " </p>",
    " </div>",
    " <div class=\"block foc drugH1Div\" id=\"F135448\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosage Forms: U.S.",
    " </span>",
    " <p style=\"text-indent:0em;text-align:justify;display:inline\">",
    " Excipient information presented when available (limited, particularly for
    generics); consult specific product labeling.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Injection, solution [preservative free]:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Kineret&reg;: 100 mg/0.67 mL (0.67 mL) [contains edetate disodium, natural
    rubber/natural latex in packaging, polysorbate 80]",
    " </p>",
    " </div>",
    " <div class=\"block geq drugH1Div\" id=\"F135434\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Generic Equivalent Available: U.S.",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " No",
    " </p>",
    " </div>",
    " <div class=\"block adm drugH1Div\" id=\"F135450\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Administration",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " SubQ: Inject into outer area of upper arms, abdomen (do not use within 2
    inches of belly button), front of middle thighs, or upper outer buttocks. Rotate
    injection sites. Allow solution to warm to room temperature prior to use (30
    minutes). Do not shake. Provided in single-use, preservative free syringes with 27-
    gauge needles; discard any unused portion. When used for the treatment of neonatal-
    onset multisystem inflammatory disease (NOMID), once-daily administration is
    preferred; however, the dose may also be divided and administered twice daily.",
    " </p>",
    " <p style=\"text-indent:0em;margin-top:2em;\">",
    " pH: 6.5 (solution in syringe)",
    " </p>",
    " </div>",
    " <div class=\"block use drugH1Div\" id=\"F135449\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Use",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Treatment of moderately- to severely-active rheumatoid arthritis (RA) in
    adult patients who have failed one or more disease-modifying antirheumatic drugs
    (DMARDs; may be used alone or in combination with DMARDs [other than tumor necrosis
    factor-blocking agents]); treatment of neonatal-onset multisystem inflammatory
    disease (NOMID), which is a cryopyrin-associated periodic syndrome (CAPS)",
    " </p>",
    " </div>",
    " <div class=\"block mst drugH1Div\" id=\"F135491\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Medication Safety Issues",
    " </span>",
    " <div class=\"collapsible\">",
    " <span class=\"collapsible-title\">",
    " Sound-alike/look-alike issues:",
    " </span>",
    " <div class=\"collapsible-wrap\">",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Anakinra may be confused with amikacin, Ampyra&trade;",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Kineret&reg; may be confused with Amikin&reg;",
    " </p>",
    " </div>",
    " </div>",
    " </div>",
    " <div class=\"block ars drugH1Div\" id=\"F135482\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Adverse Reactions Significant",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " &gt;10%:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Central nervous system: Headache (12% to 14%), fever (12%)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Gastrointestinal: Nausea (8%)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Local: Injection site reaction (RA: &le;71%; mild: 73%; moderate; 24%;
    severe: 3%; NOMID: 16%)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Neuromuscular &amp; skeletal: Arthralgia (6% to 12%)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Respiratory: Nasopharyngitis (12%)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Miscellaneous: Infection (39% versus 37% in placebo; serious infection 2% to
    3%)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " 1% to 10%:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Gastrointestinal: Diarrhea (7%)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Hematologic: Neutropenia (5% to 8%)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " &lt;1% (Limited to important or life-threatening): Cellulitis,
    hypersensitivity reactions (including anaphylaxis, angioedema, pruritus, rash,
    urticaria), leukopenia, opportunistic infection, pneumonia (bacterial), pulmonary
    fibrosis, secondary malignancies (including lymphoma, melanoma), thrombocytopenia",
    " </p>",
    " </div>",
    " <div class=\"block coi drugH1Div\" id=\"F135453\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Contraindications",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Hypersensitivity to",
    " <i>",
    " E. coli",
    " </i>",
    " -derived proteins, anakinra, or any component of the formulation",
    " </p>",
    " </div>",
    " <div class=\"block war drugH1Div\" id=\"F135438\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Warnings/Precautions",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " <i>",
    " Concerns related to adverse effects:",
    " </i>",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Anaphylaxis/hypersensitivity reactions: Hypersensitivity reactions,
    including anaphylactic reactions and angioedema, have been reported; discontinue
    use if severe hypersensitivity occurs; medications for the treatment of
    hypersensitivity reactions should be available for immediate use.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Infections: Associated with an increased risk of infection in
    rheumatoid arthritis studies. Anakinra should not be initiated in patients with an
    active infection. Patients who develop a new infection while undergoing treatment
    should be monitored closely. If a patient receiving anakinra for rheumatoid
    arthritis develops a serious infection, therapy should be discontinued; if a
    patient receiving anakinra for neonatal-onset multisystem inflammatory disease
    (NOMID) develops a serious infection, the risk of a NOMID flare should be weighed
    against the risks associated with continued treatment. Safety and efficacy have not
    been evaluated in immunosuppressed patients or patients with chronic infections;
    the impact on active or chronic infections has not been determined.
    Immunosuppressive therapy (including anakinra) may lead to reactivation of latent
    tuberculosis or other atypical or opportunistic infections; test patients for
    latent TB prior to initiation, and treat latent TB infection prior to use.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Injection site reactions: Injection site reactions commonly occur and
    are generally mild with a duration of 14-28 days.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Malignancy: May affect defenses against malignancies; impact on the
    development and course of malignancies is not fully defined. As compared to the
    general population, an increased risk of lymphoma has been noted in clinical
    trials; however, rheumatoid arthritis has been previously associated with an
    increased rate of lymphoma.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Neutropenia: A decrease in neutrophil count may occur during
    treatment. Assess neutrophil count at baseline, monthly for 3 months, then every 3
    months for up to 1 year. In a limited number of patients with NOMID, neutropenia
    resolved over time with continued anakinra administration.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " <i>",
    " Disease-related concerns:",
    " </i>",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Asthma: Use with caution in patients with asthma; may have increased
    risk of serious infection.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Renal impairment: Use caution in patients with renal impairment;
    extended dosing intervals (every other day) are recommended for severe renal
    insufficiency (Cl",
    " <sub>",
    " cr",
    " </sub>",
    " &lt;30 mL/minute) and ESRD.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " <i>",
    " Concurrent drug therapy issues:",
    " </i>",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Drug-drug interactions: Potentially significant interactions may
    exist, requiring dose or frequency adjustment, additional monitoring, and/or
    selection of alternative therapy. Consult drug interactions database for more
    detailed information.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; TNF-blocking agents: Use is not recommended in combination with tumor
    necrosis factor antagonists.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " <i>",
    " Special populations:",
    " </i>",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Elderly: Use caution due to the potential higher risk for
    infections.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " <i>",
    " Dosage form specific issues:",
    " </i>",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Latex: The packaging (needle cover) contains latex.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " <i>",
    " Other warnings/precautions:",
    " </i>",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Immunizations: Patients should be brought up to date with all
    immunizations before initiating therapy; live vaccines should not be given
    concurrently. There is no data available concerning the effects of therapy on
    vaccination or secondary transmission of live vaccines in patients receiving
    therapy.",
    " </p>",
    " </div>",
    " <div class=\"block cyt drugH1Div\" id=\"F13298752\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Metabolism/Transport Effects",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " None known.",
    " </p>",
    " </div>",
    " <div class=\"block dri drugH1Div\" id=\"F135442\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Drug Interactions",
    " </span>",
    " <br/>",
    " <br/>",
    " <div class=\"lexi\" id=\"lexiInteractAddInfo\">",
    " (For additional information:",
    " <a class=\"dip\" href=\"./drug-interaction\" target=\"_blank\">",
    " Launch Lexi-Interact&trade; Drug Interactions Program",
    " </a>",
    " )",
    " </div>",
    " <div class=\"lexi\" id=\"lexiInteractImgB\">",
    " <img border=\"0\" height=\"17\"
    src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\" width=\"71\"/>",
    " </div>",
    " <div class=\"clear\">",
    " </div>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Abatacept: Anakinra may enhance the adverse/toxic effect of Abatacept.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Anti-TNF Agents: May enhance the adverse/toxic effect of Anakinra. An
    increased risk of serious infection during concomitant use has been reported.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " BCG: Immunosuppressants may diminish the therapeutic effect of BCG.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Canakinumab: Interleukin-1 Receptor Antagonist may enhance the adverse/toxic
    effect of Canakinumab. Whether such a combination will also alter the therapeutic
    response to one or both agents is unclear.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Coccidioidin Skin Test: Immunosuppressants may diminish the diagnostic effect
    of Coccidioidin Skin Test.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Denosumab: May enhance the adverse/toxic effect of Immunosuppressants.
    Specifically, the risk for serious infections may be increased.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Echinacea: May diminish the therapeutic effect of Immunosuppressants.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of
    Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia,
    agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider
    not using a leflunomide loading dose in patients receiving other
    immunosuppressants. Patients receiving both leflunomide and another
    immunosuppressant should be monitored for bone marrow suppression at least
    monthly.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of
    Natalizumab. Specifically, the risk of concurrent infection may be increased.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Roflumilast: May enhance the immunosuppressive effect of
    Immunosuppressants.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of
    Sipuleucel-T.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Tacrolimus (Topical): May enhance the adverse/toxic effect of
    Immunosuppressants.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Tofacitinib: Anakinra may enhance the adverse/toxic effect of Tofacitinib.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Trastuzumab: May enhance the neutropenic effect of Immunosuppressants.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic
    effect of Vaccines (Inactivated).",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of
    Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish
    the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism
    vaccines with immunosuppressants; live-attenuated vaccines should not be given for
    at least 3 months after immunosuppressants.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " </div>",
    " <div class=\"block prf drugH1Div\" id=\"F135444\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pregnancy Risk Factor",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " B (",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?16/42/17068\">",
    " show table",
    " </a>",
    " )",
    " </p>",
    " </div>",
    " <div class=\"block pri drugH1Div\" id=\"F135456\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pregnancy Implications",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Animal reproduction studies have not revealed any evidence of impaired
    fertility or harm to fetus. Women exposed to anakinra during pregnancy may contact
    the Organization of Teratology Information Services (OTIS), Rheumatoid Arthritis
    and Pregnancy Study at 1-877-311-8972.",
    " </p>",
    " </div>",
    " <div class=\"block lac drugH1Div\" id=\"F135473\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Lactation",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Excretion in breast milk unknown/use caution",
    " </p>",
    " </div>",
    " <div class=\"block brc drugH1Div\" id=\"F135457\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Breast-Feeding Considerations",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Endogenous interleukin-1 receptor antagonist can be found in breast milk;
    although specific excretion of anakinra is not known. Use caution if administering
    to a nursing woman.",
    " </p>",
    " </div>",
    " <div class=\"block fee drugH1Div\" id=\"F135455\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pricing: U.S. (Medi-Span&reg;)",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Solution",
    " </b>",
    " (Kineret Subcutaneous)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " 100 mg/0.67 mL (0.67 mL): $88.46",
    " </p>",
    " </div>",
    " <div class=\"block mop drugH1Div\" id=\"F135446\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Monitoring Parameters",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " CBC with differential (baseline, then monthly for 3 months, then every 3
    months for a period up to 1 year); TB test (baseline); serum creatinine;
    signs/symptoms of infection",
    " </p>",
    " </div>",
    " <div class=\"list fbnlist drugH1Div drugBrandNames\" id=\"F135458\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " International Brand Names",
    " </span>",
    " <ul>",
    " <li>",
    " Kineret (AT, AU, CZ, DE, DK, EE, FI, FR, GB, GR, IE, IL, IT, NL, NO, PT,
    SE)",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"block pha drugH1Div\" id=\"F135437\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Mechanism of Action",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Antagonist of the interleukin-1 (IL-1) receptor. Endogenous IL-1 is induced
    by inflammatory stimuli and mediates a variety of immunological responses,
    including degradation of cartilage (loss of proteoglycans) and stimulation of bone
    resorption.",
    " </p>",
    " </div>",
    " <div class=\"block phk drugH1Div\" id=\"F135452\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pharmacodynamics/Kinetics",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Bioavailability: SubQ: 95%",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Half-life elimination: Terminal: 4-6 hours; Severe renal impairment (Cl",
    " <sub>",
    " cr",
    " </sub>",
    " &lt;30 mL/minute): ~7 hours; ESRD: 9.7 hours (Yang, 2003)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Time to peak: SubQ: 3-7 hours",
    " </p>",
    " </div>",
    " </div>",
    " <div id=\"topicAgreement\">",
    " Use of UpToDate is subject to the",
    " <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
    target=\"_blank\">",
    " Subscription and License Agreement",
    " </a>",
    " .",
    " </div>",
    " <div class=\"headingAnchor\" id=\"references\">",
    " <h1>",
    " REFERENCES",
    " </h1>",
    " <ol id=\"reference\">",
    " <li>",
    " <div class=\"reference\">",
    " Cohen S, Hurd E, Cush J, et al, &ldquo;Treatment of Rheumatoid Arthritis
    With Anakinra, a Recombinant Human Interleukin-1 Receptor Antagonist, in
    Combination With Methotrexate: Results of a Twenty-Four-Week, Multicenter,
    Randomized, Double-Blind, Placebo-Controlled Trial,&rdquo;",
    " <i>",
    " Arthritis Rheum",
    " </i>",
    " , 2002, 46(3):614-24.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?0/18/294/abstract-text/11920396/pubmed\" id=\"11920396\"
    target=\"_blank\">",
    " 11920396",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Fleischmann RM, Schechtman J, Bennett R, et al, &ldquo;Anakinra, a
    Recombinant Human Interleukin-1 Receptor Antagonist (r-metHuIL-1ra), in Patients
    With Rheumatoid Arthritis: A Large, International, Multicenter, Placebo-Controlled
    Trial,&rdquo;",
    " <i>",
    " Arthritis Rheum",
    " </i>",
    " , 2003, 48(4):927-34.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?0/18/294/abstract-text/12687534/pubmed\" id=\"12687534\"
    target=\"_blank\">",
    " 12687534",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Fleischmann RM, Tesser J, Schiff MH, et al, Safety of Extended Treatment
    With Anakinra in Patients With Rheumatoid Arthritis,",
    " <i>",
    " Ann Rheum Dis",
    " </i>",
    " , 2006,65(8):1006-12.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?0/18/294/abstract-text/16396977/pubmed\" id=\"16396977\"
    target=\"_blank\">",
    " 16396977",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Genovese MC, Cohen S, Moreland L, et al, &ldquo;Combination Therapy With
    Etanercept and Anakinra in the Treatment of Patients With Rheumatoid Arthritis Who
    Have Been Treated Unsuccessfully With Methotrexate,&rdquo;",
    " <i>",
    " Arthritis Rheum",
    " </i>",
    " , 2004, 50(5):1412-9.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?0/18/294/abstract-text/15146410/pubmed\" id=\"15146410\"
    target=\"_blank\">",
    " 15146410",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Rigante D, Leone A, Marrocco R, et al, &ldquo;Long-Term Response After 6-
    Year Treatment With Anakinra and Onset of Focal Bone Erosion in Neonatal-Onset
    Multisystem Inflammatory Disease (NOMID/CINCA),&rdquo;",
    " <i>",
    " Rheumatol Int",
    " </i>",
    " , 2011, 31(12):1661-4.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?0/18/294/abstract-text/21240490/pubmed\" id=\"21240490\"
    target=\"_blank\">",
    " 21240490",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Sibley CH, Plass N, Snow J, et al,&rdquo; Sustained Response and Prevention
    of Damage Progression in Patients With Neonatal-Onset Multisystem Inflammatory
    Disease Treated With Anakinra: A Cohort Study to Determine Three- and Five-Year
    Outcomes,&rdquo;",
    " <i>",
    " Arthritis Rheum",
    " </i>",
    " , 2012, 64(7):2375-86.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?0/18/294/abstract-text/22294344/pubmed\" id=\"22294344\"
    target=\"_blank\">",
    " 22294344",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Yang B, Baughman S, and Sullivan JT, &ldquo;Pharmacokinetics of Anakinra in
    Subjects With Different Levels of Renal Function,&rdquo;",
    " <i>",
    " Clin Pharmacol Ther",
    " </i>",
    " , 2003, 74(1):85-94.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?0/18/294/abstract-text/12844139/pubmed\" id=\"12844139\"
    target=\"_blank\">",
    " 12844139",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " </ol>",
    " </div>",
    " <div id=\"topicVersionRevision\">",
    " Topic 9246 Version 36.0",
    " </div>",
    " </div>",
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    var script_f0_18_294=[""].join("\n");
    var outline_f0_18_294=[" <div id=\"toggleOutline\">",
    " <a href=\"#\" title=\"Collapse Topic Outline\">",
    " <img alt=\"\" src=\"./../images/orange_arrow_left.myextg\"/>",
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    " <div id=\"innerOutline\">",
    " <h1>",
    " TOPIC OUTLINE",
    " </h1>",
    " <div id=\"outline\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F135465\">",
    " Brand Names: U.S.",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F135466\">",
    " Brand Names: Canada",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F135484\">",
    " Pharmacologic Category",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F135468\">",
    " Dosing: Adult",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F16330957\">",
    " Dosing: Pediatric",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F135469\">",
    " Dosing: Geriatric",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F135470\">",
    " Dosing: Renal Impairment",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F13258473\">",
    " Dosing: Hepatic Impairment",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F135448\">",
    " Dosage Forms: U.S.",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F135434\">",
    " Generic Equivalent Available: U.S.",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F135450\">",
    " Administration",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F135449\">",
    " Use",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F135491\">",
    " Medication Safety Issues",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F135482\">",
    " Adverse Reactions Significant",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F135453\">",
    " Contraindications",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F135438\">",
    " Warnings/Precautions",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F13298752\">",
    " Metabolism/Transport Effects",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F135442\">",
    " Drug Interactions",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F135444\">",
    " Pregnancy Risk Factor",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F135456\">",
    " Pregnancy Implications",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F135473\">",
    " Lactation",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F135457\">",
    " Breast-Feeding Considerations",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F135455\">",
    " Pricing: U.S. (Medi-Span&reg;)",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F135446\">",
    " Monitoring Parameters",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F135458\">",
    " International Brand Names",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F135437\">",
    " Mechanism of Action",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F135452\">",
    " Pharmacodynamics/Kinetics",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " <div class=\"openRelatedGraphics\" id=\"DRUG_GEN/9246\" rel=\"outline_link\">",
    " GRAPHICS",
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    " TABLES",
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    " </div>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?23/39/24183\"
    title=\"Lexicomp clinical abbreviations\">",
    " Lexicomp clinical abbreviations",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
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    " </h1>",
    " <div id=\"relatedTopics\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?0/10/163?
    source=related_link\">",
    " Anakinra: Patient drug information",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_pediatric\" href=\"UTD.htm?32/52/33605?
    source=related_link\">",
    " Anakinra: Pediatric drug information",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " </div>"].join("\n");
    var title_f0_18_295="OnabotulinumtoxinA (botulinum toxin type A, Botox): Pediatric
    drug information";
    var content_f0_18_295=[" <noscript>",
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    " <!-- TC:TOPIC_PAGE -->",
    " <div id=\"topicContent\">",
    " <div id=\"drugTitle\">",
    " OnabotulinumtoxinA (botulinum toxin type A, Botox): Pediatric drug
    information",
    " </div>",
    " <div id=\"lexiTitleImg\">",
    " <img height=\"17\" src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\"
    width=\"71\"/>",
    " </div>",
    " <div class=\"clear\">",
    " </div>",
    " <div id=\"drugCopy\">",
    " Copyright 1978-2013 Lexicomp, Inc. All rights reserved.",
    " </div>",
    " <div id=\"topicText\">",
    " (For additional information",
    " <a class=\"drug drug_general\" href=\"UTD.htm?10/27/10681?source=see_link\">",
    " see \"OnabotulinumtoxinA (botulinum toxin type A, Botox): Drug information\"",
    " </a>",
    " and",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?15/55/16245?source=see_link\">",
    " see \"OnabotulinumtoxinA (botulinum toxin type A, Botox): Patient drug
    information\"",
    " </a>",
    " )",
    " <br/>",
    " For abbreviations and symbols that may be used in Lexicomp (",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?23/39/24183\">",
    " show table",
    " </a>",
    " )",
    " <div class=\"block black-box-warn drugH1Div\" id=\"F9605655\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " ALERT: U.S. Boxed Warning",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " The FDA-approved labeling includes a boxed warning. See Warnings/Precautions
    section for a concise summary of this information. For verbatim wording of the
    boxed warning, consult the product labeling or",
    " <a href=\"file://www.fda.gov\" target=\"_blank\">",
    " www.fda.gov",
    " </a>",
    " .",
    " </p>",
    " </div>",
    " <div class=\"list ubnlist drugH1Div drugBrandNames\" id=\"F141936\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Brand Names: U.S.",
    " </span>",
    " <ul>",
    " <li>",
    " Botox&reg;;",
    " </li>",
    " <li>",
    " Botox&reg; Cosmetic",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"list cbnlist drugH1Div drugBrandNames\" id=\"F141937\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Brand Names: Canada",
    " </span>",
    " <ul>",
    " <li>",
    " Botox&reg;;",
    " </li>",
    " <li>",
    " Botox&reg; Cosmetic",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"list_set htclist drugH1Div drugBrandNames\" id=\"F1056907\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Therapeutic Category",
    " </span>",
    " <ul>",
    " <li>",
    " <span class=\"list-set-name\">",
    " Muscle Contracture, Treatment",
    " </span>",
    " </li>",
    " <li>",
    " <span class=\"list-set-name\">",
    " Ophthalmic Agent, Toxin",
    " </span>",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"block dos drugH1Div\" id=\"F1056900\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Usual",
    " </span>",
    " <p>",
    " (For additional information",
    " <a class=\"drug drug_general\" href=\"UTD.htm?10/27/10681?
    source=see_link\">",
    " see \"OnabotulinumtoxinA (botulinum toxin type A, Botox): Drug
    information\"",
    " </a>",
    " )",
    " </p>",
    " <p style=\"text-indent:0em;display:inline\">",
    " I.M.:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Strabismus:",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Children 2 months to 12 years:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Horizontal or vertical deviations &lt;20 prism diopters: 1.25 units into any
    one muscle",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Horizontal or vertical deviations 20-25 prism diopters: 1-2.5 units into any
    one muscle",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Persistent VI nerve palsy of &ge;1 month duration: 1-1.25 units into the
    medial rectus muscle",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Children &ge;12 years and Adults:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Horizontal or vertical deviations &lt;20 prism diopters: 1.25-2.5 units into
    any one muscle",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Horizontal or vertical deviations 20-50 prism diopters: 2.5-5 units into any
    one muscle",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Persistent VI nerve palsy of &ge;1 month duration: 1.25-2.5 units into the
    medial rectus muscle",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " <b>",
    " Note:",
    " </b>",
    " Re-examine patient 7-14 days after each injection to assess effects; dosage
    may be increased up to twofold of the previously administered dose; do not exceed
    25 units as a single injection for any one muscle",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Spasticity associated with cerebral palsy:",
    " </b>",
    " Children &gt;18 months to Adolescents: Small muscle: 1-2 units/kg; large
    muscle: 3-6 units/kg; maximum dose per injection site: 50 units; maximum dose for
    any one visit: 12 units/kg, up to 400 units; no more than 400 units should be
    administered during a 3-month period",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Blepharospasm:",
    " </b>",
    " Adults: Initial: 1.25-2.5 units injected into the medial and lateral
    pretarsal orbicularis oculi of the upper lid and into the lateral pretarsal
    orbicularis oculi of the lower lid; dose may be increased up to 2.5-5 units at
    repeat treatment sessions; do not exceed 5 units per injection or cumulative dose
    of 200 units in a 30-day period",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Cervical dystonia:",
    " </b>",
    " Adults: Initial and sequential doses should be individualized related to the
    patient's head and neck position, localization of pain, muscle hypertrophy, and
    patient response; mean dosage used in research trials: 236 units (range: 198-300
    units) (maximum: &le;50 units/site) divided among affected muscles; limit total
    dose into sternocleidomastoid muscles to &le;100 units to decrease the occurrence
    of dysphagia",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Severe primary axillary hyperhidrosis:",
    " </b>",
    " Adults: Intradermal: 50 units per axilla injected in 0.1-0.2 mL aliquots",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Reduction of glabellar lines:",
    " </b>",
    " Adults &le;65 years: I.M.: An effective dose is determined by gross
    observation of the patient's ability to activate the superficial muscles injected.
    The location, size and use of muscles may vary markedly among individuals. Inject
    0.1 mL dose into each of five sites, two in each corrugator muscle and one in the
    procerus muscle (total dose 0.5 mL).",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Chronic migraine:",
    " </b>",
    " Adults: I.M.: Administer 5 units/0.1 mL per site. Recommended total dose is
    155 units once every 12 weeks. Each 155-unit dose should be equally divided and
    administered bilaterally, into 31 total sites as described below (refer to
    prescribing information for specific diagrams of recommended injection sites):",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Corrugator: 5 units to each side (2 sites)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Procerus: 5 units (1 site only)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Frontalis: 10 units to each side (divided into 2 sites/side)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Temporalis: 20 units to each side (divided into 4 sites/side)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Occipitalis: 15 units to each side (divided into 3 sites/side)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Cervical paraspinal: 10 units to each side (divided into 2 sites/side)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Trapezius: 15 units to each side (divided into 3 sites/side)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Spasticity (focal):",
    " </b>",
    " Adults: I.M.: Individualize dose based on patient size, extent, and location
    of muscle involvement, degree of spasticity, local muscle weakness, and response to
    prior treatment. In clinical trials, total doses up to 360 units were administered
    as separate injections typically divided among selected muscles; may repeat therapy
    at &ge;3 months with appropriate dosage based upon the clinical condition of
    patient at time of retreatment.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Suggested guidelines for the treatment of upper limb spasticity. The lowest
    recommended starting dose should be used and &le;50 units/site should be
    administered.",
    " <b>",
    " Note:",
    " </b>",
    " Dose listed is total dose administered as individual or separate
    intramuscular injection(s):",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Biceps brachii: 100-200 units (up to 4 sites)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Flexor digitorum profundus: 30-50 units (1 site)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Flexor digitorum sublimes: 30-50 units (1 site)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Flexor carpi radialis: 12.5-50 units (1 site)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Flexor carpi ulnaris: 12.5-50 units (1 site)",
    " </p>",
    " </div>",
    " <div class=\"block foc drugH1Div\" id=\"F141917\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosage Forms: U.S.",
    " </span>",
    " <p style=\"text-indent:0em;text-align:justify;display:inline\">",
    " Excipient information presented when available (limited, particularly for
    generics); consult specific product labeling.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Injection, powder for reconstitution [preservative free]:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Botox&reg;:",
    " <i>",
    " Clostridium botulinum",
    " </i>",
    " type A neurotoxin complex 100 units,",
    " <i>",
    " Clostridium botulinum",
    " </i>",
    " type A neurotoxin complex 200 units [contains albumin (human)]",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Botox&reg; Cosmetic:",
    " <i>",
    " Clostridium botulinum",
    " </i>",
    " type A neurotoxin complex 100 units,",
    " <i>",
    " Clostridium botulinum",
    " </i>",
    " type A neurotoxin complex 50 units [contains albumin (human)]",
    " </p>",
    " </div>",
    " <div class=\"block geq drugH1Div\" id=\"F141903\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Generic Equivalent Available: U.S.",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " No",
    " </p>",
    " </div>",
    " <div class=\"block meg drugH1Div\" id=\"F8104244\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Medication Guide",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " An FDA-approved patient medication guide, which is available with the product
    information and at",
    " <a href=\"file://www.fda.gov/downloads/Drugs/DrugSafety/UCM176360.pdf\"
    target=\"_blank\">",
    " file://www.fda.gov/downloads/Drugs/DrugSafety/UCM176360.pdf",
    " </a>",
    " , must be dispensed with this medication.",
    " </p>",
    " </div>",
    " <div class=\"block adm drugH1Div\" id=\"F1056910\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Administration",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Parenteral: For I.M. or intradermal administration only by individuals
    understanding the relevant neuromuscular and orbital anatomy and any alterations to
    the anatomy due to prior surgical procedures and standard electromyographic
    techniques; reconstitute vial with preservative-free NS to obtain an optimal
    injection volume of 0.1 mL; suggested diluent volumes and resulting concentrations:
    1 mL (10 units/0.1 mL); 2 mL (5 units/0.1 mL), 4 mL (2.5 units/0.1 mL) or 8 mL
    (1.25 units/0.1 mL); gently swirl as onabotulinumtoxinA is denatured by violent
    agitation. Local site reactions may be minimized by careful injection into the
    target muscle, using a minimal volume, and slowing the rate of injection.
    Application of ice and topical anesthetics to the injection site may also be
    used.",
    " </p>",
    " </div>",
    " <div class=\"block sta drugH1Div\" id=\"F1056903\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Stability",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Store lyophilized product in refrigerator at 2&deg;C to 8&deg;C (36&deg;F to
    46&deg;F); administer within 24 hours after reconstitution; reconstituted solution
    may be stored in the refrigerator (2&deg;C to 8&deg;C/36&deg;F to 46&deg;F) until
    administered; do not freeze reconstituted solution",
    " </p>",
    " </div>",
    " <div class=\"block use drugH1Div\" id=\"F1056909\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Use",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Treatment of strabismus and blepharospasm associated with dystonia (including
    benign essential blepharospasm or VII nerve disorders) (FDA approved in ages &gt;12
    years and adults); treatment of dynamic muscle contracture in pediatric cerebral
    palsy patients (orphan drug); treatment of cervical dystonia (FDA approved in ages
    &gt;16 and adults); treatment of severe primary axillary hyperhidrosis (not
    adequately controlled with topical treatments) (FDA approved in adults); temporary
    improvement in the appearance of lines and wrinkles of the face (moderate to severe
    glabellar lines associated with corrugator and/or procerus muscle activity) in
    adult patients &le;65 years of age; focal spasticity, specifically upper limb
    spasticity (FDA approved in adults); prophylaxis of chronic migraine headache
    (&ge;15 days/month with &ge;4 hours/day headache duration) (FDA approved in
    adults). Other uses include treatment of sialorrhea, palmar hyperhidrosis,
    esophageal achalasia, chronic anal fissure.",
    " </p>",
    " </div>",
    " <div class=\"block mst drugH1Div\" id=\"F7728706\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Medication Safety Issues",
    " </span>",
    " <div class=\"collapsible\">",
    " <span class=\"collapsible-title\">",
    " Other safety concerns:",
    " </span>",
    " <div class=\"collapsible-wrap\">",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " Botulinum products are not interchangeable; potency differences may exist
    between the products.",
    " </p>",
    " </div>",
    " </div>",
    " </div>",
    " <div class=\"block arm drugH1Div\" id=\"F6474810\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Adverse Reactions",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Adverse effects usually occur in 1 week and may last up to several months.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;margin-top:2em;text-
    align:justify;\">",
    " <i>",
    " Bladder dysfunction:",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Gastrointestinal: Constipation",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Genitourinary: Bacteriuria, dysuria, hematuria, residual urine volume
    increased (not requiring catheterization), urinary retention, urinary tract
    infection",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Neuromuscular &amp; skeletal: Gait disturbance, muscle spasm, muscular
    weakness",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;margin-top:0em;text-
    align:justify;\">",
    " <i>",
    " Cerebral palsy spasticity:",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Central nervous system: Fever, lethargy, pain",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Neuromuscular &amp; skeletal: Falling, weakness",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;margin-top:0em;text-
    align:justify;\">",
    " <i>",
    " Cervical dystonia:",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Central nervous system: Dizziness, drowsiness, fever, headache, malaise,
    pain, speech disorder",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Gastrointestinal: Dysphagia, nausea, xerostomia",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Local: Injection site reaction: Soreness",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Neuromuscular &amp; skeletal: Back pain, focal weakness, hypertonia, neck
    pain, numbness, stiffness, weakness",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Ocular: Diplopia, ptosis",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Respiratory: Cough, dyspnea, rhinitis, upper respiratory infection",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Miscellaneous: Flu-like syndrome",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <i>",
    " Chronic migraines:",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Cardiovascular: Hypertension",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Central nervous system: Facial paresis, Headache, worsening migraine",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Neuromuscular &amp; skeletal: Muscle spasm, musculoskeletal pain, myalgia,
    neck pain, stiffness, weakness",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Ocular: Eyelid ptosis",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Respiratory: Bronchitis",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Miscellaneous: Injection site pain",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <i>",
    " Focal spasticity:",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Central nervous system: Fatigue",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Gastrointestinal: Nausea",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Neuromuscular &amp; skeletal: Pain in extremity, weakness",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Respiratory: Bronchitis",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <i>",
    " Other indications (blepharospasm, primary axillary hyperhidrosis, reduction
    of glabellar lines, strabismus):",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Cardiovascular: Hypertension",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Central nervous system: Anxiety, dizziness, fever, headache, pain",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Dermatologic: Pruritus, rash, skin tightness",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Gastrointestinal: Dyspepsia, nausea",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Local: Injection site reaction: Hemorrhage, pain, soreness",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Neuromuscular &amp; skeletal: Back pain, facial pain, neck pain, weakness",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Ocular: Diplopia, irritation/tearing (includes dry eye, lagophthalmos,
    photophobia); keratitis, ptosis, superficial punctate keratitis",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Respiratory: Pharyngitis",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Miscellaneous: Flu-like syndrome, infection, nonaxillary sweating",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;margin-top:2em;text-
    align:justify;\">",
    " <b>",
    " Rare but important and life-threatening:",
    " </b>",
    " <i>",
    " Any indication:",
    " </i>",
    " Abdominal distension, abdominal pain, abnormal dreams, acute angle closure
    glaucoma, allergic reactions, alopecia, anaphylaxis, ankle pain, anorexia, anterior
    segment eye ischemia, appetite decreased, arrhythmia, arthralgia, aspiration
    pneumonia, asthma, autonomic dysreflexia, blurred vision, brachial plexopathy,
    cardiovascular insufficiency, ciliary ganglion damage, circulatory collapse,
    colitis, conjunctivitis, corneal perforation, denervation, dermatitis, dermatitis
    psoriasiform, diaphoresis, diarrhea, dysarthria, dysphonia, ectropion, entropion,
    erythema, erythema multiforme, eye edema, eye pain, eyelid edema, facial palsy,
    facial weakness, fatigue, focal facial paralysis, glaucoma, hearing loss, herpes
    zoster, hypoacusis, hypoesthesia, injection site inflammation, knee pain, leg
    cramps, lethargy, lymphadenopathy, madarosis, MI, muscle atrophy, myalgia,
    myasthenia gravis exacerbation, neutralizing antibody formation, numbness (local),
    paresthesia, peripheral edema, peripheral neuropathy, pneumonia, psoriasiform
    eruption, radiculopathy, reduced blinking leading to corneal ulceration,
    respiratory depression, respiratory failure, retinal vein occlusion, retrobulbar
    hemorrhage, seizure, somnolence, syncope, tinnitus, tremor, trismus, urticaria,
    vertigo with nystagmus, visual disturbances, vitreous hemorrhage, vomiting",
    " </p>",
    " </div>",
    " <div class=\"block coi drugH1Div\" id=\"F1056913\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Contraindications",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Hypersensitivity to botulinum toxin or any component of the formulation;
    infection at the site of injection",
    " </p>",
    " </div>",
    " <div class=\"block pre drugH1Div\" id=\"F1056899\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Precautions",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Presence of antibodies to onabotulinumtoxinA may reduce the effectiveness of
    therapy; to minimize the development of antibodies, keep the dose of
    onabotulinumtoxinA as low as possible. Reduced blinking from onabotulinumtoxinA
    injection of the orbicularis muscle can lead to corneal exposure, persistent
    epithelial defect, and corneal ulceration, especially in patients with VII nerve
    disorders; carefully test corneal sensation in eyes previously operated upon. Avoid
    injection into the lower lid area to avoid ectropion, and vigorously treat any
    epithelial defect (this may require protective drops, ointment, therapeutic soft
    contact lenses, or closure of the eye by patching). Retrobulbar hemorrhages
    sufficient to compromise retinal circulation have occurred from needle penetrations
    into the orbit; have appropriate instruments to decompress the orbit accessible;
    ocular (globe) penetrations by needles have also occurred (an ophthalmoscope to
    diagnose this condition should be available).",
    " </p>",
    " <p style=\"text-indent:0em;margin-top:2em;text-align:justify;\">",
    " Use with caution in patients with peripheral motor neuropathic diseases (eg,
    amyotrophic lateral sclerosis or motor neuropathy) or neuromuscular junction
    disorders (eg, myasthenia gravis or Lambert-Eaton syndrome) as these patients may
    be at increased risk for development of significant systemic side effects including
    severe dysphagia and respiratory compromise; use cautiously if there is
    inflammation present at the proposed injection site or when excessive weakness or
    atrophy is present in the target muscles",
    " </p>",
    " </div>",
    " <div class=\"block war drugH1Div\" id=\"F1056898\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Warnings",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " The U.S. Food and Drug Administration (FDA) and Health Canada have issued
    respective early communications to healthcare professionals alerting them of
    serious adverse events (including fatalities) in association with the use of
    onabotulinumtoxinA (Botox&reg;, Botox&reg; Cosmetic) and rimabotulinumtoxinB
    (Myobloc&reg;). Events reported are suggestive of botulism, indicating systemic
    spread of the botulinum toxin beyond the site of injection. Reactions were observed
    in both adult and pediatric patients treated for a variety of conditions with
    varying doses. However, the most serious outcomes, including respiratory failure
    and death, were associated with the use in children for cerebral palsy limb
    spasticity. The FDA has evaluated postmarketing cases and now reports that systemic
    and potentially fatal toxicity may result from local injection of the botulinum
    toxins in the treatment of other underlying conditions such as cerebral palsy
    associated with limb spasticity. Monitor patients closely for signs/symptoms of
    systemic toxic effects (possibly occurring 1 day to several weeks after treatment)
    and instruct patients to seek immediate medical attention with worsening symptoms
    or dysphagia, dyspnea, muscle weakness, or difficulty speaking.",
    " </p>",
    " <p style=\"text-indent:0em;margin-top:2em;\">",
    " AbobotulinumtoxinA (Dysport&reg;) is not equivalent in potency to Botox&reg;;
    the Dysport&reg;:Botox&reg; equivalency ratio is ~3:1 or 4:1, respectively;
    patients treated for cervical dystonia may experience dysphagia which rarely may
    result in dyspnea, aspiration, and pneumonia; weakness of hand muscles and
    blepharoptosis may occur in patients who also receive treatment for palmar and
    facial hyperhidrosis respectively",
    " </p>",
    " </div>",
    " <div class=\"block cyt drugH1Div\" id=\"F13299790\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Metabolism/Transport Effects",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " None known.",
    " </p>",
    " </div>",
    " <div class=\"block dri drugH1Div\" id=\"F141912\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Drug Interactions",
    " </span>",
    " <br/>",
    " <br/>",
    " <div class=\"lexi\" id=\"lexiInteractAddInfo\">",
    " (For additional information:",
    " <a class=\"dip\" href=\"./drug-interaction\" target=\"_blank\">",
    " Launch Lexi-Interact&trade; Drug Interactions Program",
    " </a>",
    " )",
    " </div>",
    " <div class=\"lexi\" id=\"lexiInteractImgB\">",
    " <img border=\"0\" height=\"17\"
    src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\" width=\"71\"/>",
    " </div>",
    " <div class=\"clear\">",
    " </div>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " AbobotulinumtoxinA: OnabotulinumtoxinA may enhance the adverse neuromuscular
    effect of AbobotulinumtoxinA.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Aminoglycosides: May enhance the neuromuscular-blocking effect of
    OnabotulinumtoxinA.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Anticholinergic Agents: May enhance the anticholinergic effect of
    OnabotulinumtoxinA.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Neuromuscular-Blocking Agents: May enhance the neuromuscular-blocking effect
    of OnabotulinumtoxinA.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " RimabotulinumtoxinB: OnabotulinumtoxinA may enhance the neuromuscular-
    blocking effect of RimabotulinumtoxinB.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " </div>",
    " <div class=\"block prf drugH1Div\" id=\"F141914\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pregnancy Risk Factor",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " C (",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?16/42/17068\">",
    " show table",
    " </a>",
    " )",
    " </p>",
    " </div>",
    " <div class=\"block pri drugH1Div\" id=\"F141926\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pregnancy Implications",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Decreased fetal body weight, delayed ossification, maternal toxicity,
    abortions, and fetal malformations were observed in animal studies. Human
    reproduction studies have not been conducted. Avoid use in pregnancy. Based on
    limited case reports, adverse fetal effects have not been observed with inadvertent
    administration during pregnancy. It is currently recommended to ensure adequate
    contraception in women of childbearing potential.",
    " </p>",
    " </div>",
    " <div class=\"block mop drugH1Div\" id=\"F1056906\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Monitoring Parameters",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Monitor patients closely for signs/symptoms of systemic toxic effects
    (possibly occurring 1 day to several weeks after treatment)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Cervical dystonia: Toronto Western Spasmodic Torticollis Rating Scale
    (TWSTRS) which evaluates severity, disability, and pain",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Cerebral palsy: Modified Ashworth Scale, Tardieu Scale, Gross Motor Function
    Measure; treatment goals include: Improved gait and balance, facilitation of
    patient care, increased comfort with therapy, improved tolerance of bracing, and
    prevention of musculoskeletal complications",
    " </p>",
    " </div>",
    " <div class=\"block pha drugH1Div\" id=\"F1056897\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Mechanism of Action",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " OnabotulinumtoxinA (formerly botulinum A toxin) is a neurotoxin produced by",
    " <i>",
    " Clostridium botulinum",
    " </i>",
    " , a spore-forming anaerobic bacillus; it blocks neuromuscular conduction by
    binding to receptor sites on motor nerve terminals, entering the nerve terminals
    and inhibiting the release of acetylcholine. When injected intramuscularly at
    therapeutic doses, it produces a localized chemical denervation muscle paralysis.
    When the muscle is chemically denervated, it atrophies and may develop
    extrajunctional acetylcholine receptors. There is evidence that the nerve can
    sprout and reinnervate the muscle, with the weakness being reversible. Following
    several weeks of paralysis, alignment of the eye is measurably changed, despite
    return of innervation to the injected muscle. When injected intradermally, a
    temporary chemical denervation of the sweat gland reduces local sweating.",
    " </p>",
    " </div>",
    " <div class=\"block phd drugH1Div\" id=\"F1056912\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pharmacodynamics",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Strabismus:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Onset of action: 1-2 days after injection",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Duration of paralysis: 2-6 weeks",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Blepharospasm:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Onset of action: 3 days after injection",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Maximum effect: 1-2 weeks",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Duration of paralysis: 3 months",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Spasticity associated with cerebral palsy",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Onset of action: Several days",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Duration of paralysis: 3-8 months",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Reduction in axillary sweat production:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Duration of effect: 201 days (mean)",
    " </p>",
    " </div>",
    " <div class=\"block pai drugH1Div\" id=\"F1056905\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Patient Information",
    " </span>",
    " <p>",
    " (For additional information",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?15/55/16245?
    source=see_link\">",
    " see \"OnabotulinumtoxinA (botulinum toxin type A, Botox): Patient drug
    information\"",
    " </a>",
    " )",
    " </p>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Patients with blepharospasm may have been extremely sedentary for a long
    time; sedentary patients should be cautioned to resume activity slowly and
    carefully following injection; may cause dry mouth",
    " </p>",
    " </div>",
    " </div>",
    " <div id=\"topicAgreement\">",
    " Use of UpToDate is subject to the",
    " <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
    target=\"_blank\">",
    " Subscription and License Agreement",
    " </a>",
    " .",
    " </div>",
    " <div class=\"headingAnchor\" id=\"references\">",
    " <h1>",
    " REFERENCES",
    " </h1>",
    " <ol id=\"reference\">",
    " <li>",
    " <div class=\"reference\">",
    " &ldquo;Botulinum Toxin,&rdquo;",
    " <i>",
    " NIH Consens Statement",
    " </i>",
    " , 1990, 12-14, 8(8):1-20.",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Benson J and Daugherty KK, \"Botulinum Toxin A in the Treatment of
    Sialorrhea,\"",
    " <i>",
    " Ann Pharmacother",
    " </i>",
    " , 2007, 41(1):79-85.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?0/18/295/abstract-text/17190848/pubmed\" id=\"17190848\"
    target=\"_blank\">",
    " 17190848",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Charles PD, \"Botulinum Neurotoxin Serotype A: A Clinical Update on Non-
    cosmetic Uses,\"",
    " <i>",
    " Am J Health Syst Pharm",
    " </i>",
    " , 2004, 61(22 Suppl 6):S11-23.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?0/18/295/abstract-text/15598005/pubmed\" id=\"15598005\"
    target=\"_blank\">",
    " 15598005",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Cheng CM, Chen JS, and Patel RP, \"Unlabeled Uses of Botulinum Toxins: A
    Review, Part 1,\"",
    " <i>",
    " Am J Health Syst Pharm",
    " </i>",
    " , 2006, 63(2):145-52.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?0/18/295/abstract-text/16390928 /pubmed\"
    id=\"16390928 \" target=\"_blank\">",
    " 16390928",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Cheng CM, Chen JS, and Patel RP, \"Unlabeled Uses of Botulinum Toxins: A
    Review, Part 2,\"",
    " <i>",
    " Am J Health Syst Pharm",
    " </i>",
    " , 2006, 63(3):225-32.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?0/18/295/abstract-text/16434781/pubmed\" id=\"16434781\"
    target=\"_blank\">",
    " 16434781",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Criswell SR, Crowner BE, and Racette BA, \"The Use of Botulinum Toxin
    Therapy for Lower-Extremity Spasticity in Children With Cerebral Palsy,\"",
    " <i>",
    " Neurosurg Focus",
    " </i>",
    " , 2006, 21(2):e1.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?0/18/295/abstract-text/16918222 /pubmed\"
    id=\"16918222 \" target=\"_blank\">",
    " 16918222",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Russman BS, Tilton A, and Gormley ME Jr, &ldquo;Cerebral Palsy: A Rational
    Approach to a Treatment Protocol, and the Role of Botulinum Toxin in
    Treatment,&rdquo;",
    " <i>",
    " Muscle Nerve Suppl,",
    " </i>",
    " 1997, 6:S181-S193.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?0/18/295/abstract-text/9826990/pubmed\" id=\"9826990\"
    target=\"_blank\">",
    " 9826990",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Scott AB, Magoon EH, McNeer KW, et al, &ldquo;Botulinum Treatment of
    Childhood Strabismus,&rdquo;",
    " <i>",
    " Ophthalmology,",
    " </i>",
    " 1990, 97(11):1434-8.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?0/18/295/abstract-text/2255516 /pubmed\" id=\"2255516 \"
    target=\"_blank\">",
    " 2255516",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " </ol>",
    " </div>",
    " <div id=\"topicVersionRevision\">",
    " Topic 13089 Version 32.0",
    " </div>",
    " </div>",
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    var script_f0_18_295=[""].join("\n");
    var outline_f0_18_295=[" <div id=\"toggleOutline\">",
    " <a href=\"#\" title=\"Collapse Topic Outline\">",
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    " <div id=\"innerOutline\">",
    " <h1>",
    " TOPIC OUTLINE",
    " </h1>",
    " <div id=\"outline\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F9605655\">",
    " ALERT: U.S. Boxed Warning",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F141936\">",
    " Brand Names: U.S.",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F141937\">",
    " Brand Names: Canada",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1056907\">",
    " Therapeutic Category",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1056900\">",
    " Dosing: Usual",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F141917\">",
    " Dosage Forms: U.S.",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F141903\">",
    " Generic Equivalent Available: U.S.",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F8104244\">",
    " Medication Guide",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1056910\">",
    " Administration",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1056903\">",
    " Stability",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1056909\">",
    " Use",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F7728706\">",
    " Medication Safety Issues",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F6474810\">",
    " Adverse Reactions",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1056913\">",
    " Contraindications",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1056899\">",
    " Precautions",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1056898\">",
    " Warnings",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F13299790\">",
    " Metabolism/Transport Effects",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F141912\">",
    " Drug Interactions",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F141914\">",
    " Pregnancy Risk Factor",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F141926\">",
    " Pregnancy Implications",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1056906\">",
    " Monitoring Parameters",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1056897\">",
    " Mechanism of Action",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1056912\">",
    " Pharmacodynamics",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1056905\">",
    " Patient Information",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " <div class=\"openRelatedGraphics\" id=\"DRUG_PED/13089\"
    rel=\"outline_link\">",
    " GRAPHICS",
    " <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
    " View All",
    " </a>",
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    " <a href=\"#\" title=\"TABLES\">",
    " TABLES",
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    " </div>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?23/39/24183\"
    title=\"Lexicomp clinical abbreviations\">",
    " Lexicomp clinical abbreviations",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
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    " RELATED TOPICS",
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    " <ul>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_general\" href=\"UTD.htm?10/27/10681?
    source=related_link\">",
    " OnabotulinumtoxinA (botulinum toxin type A, Botox): Drug information",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?15/55/16245?
    source=related_link\">",
    " OnabotulinumtoxinA (botulinum toxin type A, Botox): Patient drug
    information",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " </div>"].join("\n");
    var title_f0_18_296="Amlodipine: Drug information";
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    " <!-- TC:TOPIC_PAGE -->",
    " <div id=\"topicContent\">",
    " <div id=\"drugTitle\">",
    " Amlodipine: Drug information",
    " </div>",
    " <div id=\"lexiTitleImg\">",
    " <img height=\"17\" src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\"
    width=\"71\"/>",
    " </div>",
    " <div class=\"clear\">",
    " </div>",
    " <div id=\"drugCopy\">",
    " Copyright 1978-2013 Lexicomp, Inc. All rights reserved.",
    " </div>",
    " <div id=\"topicText\">",
    " (For additional information",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?4/13/4309?source=see_link\">",
    " see \"Amlodipine: Patient drug information\"",
    " </a>",
    " and",
    " <a class=\"drug drug_pediatric\" href=\"UTD.htm?35/22/36199?
    source=see_link\">",
    " see \"Amlodipine: Pediatric drug information\"",
    " </a>",
    " )",
    " <br/>",
    " For abbreviations and symbols that may be used in Lexicomp (",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?23/39/24183\">",
    " show table",
    " </a>",
    " )",
    " <div class=\"list ubnlist drugH1Div drugBrandNames\" id=\"F133997\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Brand Names: U.S.",
    " </span>",
    " <ul>",
    " <li>",
    " Norvasc&reg;",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"list cbnlist drugH1Div drugBrandNames\" id=\"F133998\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Brand Names: Canada",
    " </span>",
    " <ul>",
    " <li>",
    " Accel-Amlodipine;",
    " </li>",
    " <li>",
    " Amlodipine-Odan;",
    " </li>",
    " <li>",
    " Apo-Amlodipine&reg;;",
    " </li>",
    " <li>",
    " CO Amlodipine;",
    " </li>",
    " <li>",
    " Dom-Amlodipine;",
    " </li>",
    " <li>",
    " GD-Amlodipine;",
    " </li>",
    " <li>",
    " JAMP-Amlodipine;",
    " </li>",
    " <li>",
    " Manda-Amlodipine;",
    " </li>",
    " <li>",
    " Mint-Amlodipine;",
    " </li>",
    " <li>",
    " Mylan-Amlodipine;",
    " </li>",
    " <li>",
    " Norvasc&reg;;",
    " </li>",
    " <li>",
    " PHL-Amlodipine;",
    " </li>",
    " <li>",
    " PMS-Amlodipine;",
    " </li>",
    " <li>",
    " Q-Amlodipine;",
    " </li>",
    " <li>",
    " RAN&trade;-Amlodipine;",
    " </li>",
    " <li>",
    " ratio-Amlodipine;",
    " </li>",
    " <li>",
    " Riva-Amlodipine;",
    " </li>",
    " <li>",
    " Sandoz Amlodipine;",
    " </li>",
    " <li>",
    " Septa-Amlodipine;",
    " </li>",
    " <li>",
    " Teva-Amlodipine;",
    " </li>",
    " <li>",
    " ZYM-Amlodipine",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"ex_sect_xr thclist drugH1Div drugBrandNames\" id=\"F134043\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pharmacologic Category",
    " </span>",
    " <ul>",
    " <li>",
    " Antianginal Agent;",
    " </li>",
    " <li>",
    " Calcium Channel Blocker;",
    " </li>",
    " <li>",
    " Calcium Channel Blocker, Dihydropyridine",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"block doa drugH1Div\" id=\"F134002\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Adult",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Hypertension:",
    " </b>",
    " Oral: Initial dose: 5 mg once daily; maximum dose: 10 mg once daily. In
    general, titrate in 2.5 mg increments over 7-14 days. Usual dosage range (JNC 7):
    2.5-10 mg once daily.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Angina:",
    " </b>",
    " Oral: Usual dose: 5-10 mg; most patients require 10 mg for adequate
    effect.",
    " </p>",
    " </div>",
    " <div class=\"block dop drugH1Div\" id=\"F134022\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Pediatric",
    " </span>",
    " <p>",
    " (For additional information",
    " <a class=\"drug drug_pediatric\" href=\"UTD.htm?35/22/36199?
    source=see_link\">",
    " see \"Amlodipine: Pediatric drug information\"",
    " </a>",
    " )",
    " </p>",
    " <p style=\"text-indent:0em;display:inline\">",
    " <b>",
    " Hypertension:",
    " </b>",
    " Oral: Children 6-17 years: 2.5-5 mg once daily",
    " </p>",
    " </div>",
    " <div class=\"block doe drugH1Div\" id=\"F134003\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Geriatric",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Dosing should start at the lower end of dosing range and titrated to response
    due to possible increased incidence of hepatic, renal, or cardiac impairment.
    Elderly patients also show decreased clearance of amlodipine.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;margin-top:0em;text-
    align:justify;\">",
    " <b>",
    " Hypertension:",
    " </b>",
    " Oral: 2.5 mg once daily",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Angina:",
    " </b>",
    " Oral: 5 mg once daily",
    " </p>",
    " </div>",
    " <div class=\"block dor drugH1Div\" id=\"F6852223\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Renal Impairment",
    " </span>",
    " <p style=\"text-indent:0em;text-align:justify;display:inline\">",
    " Dialysis: Hemodialysis and peritoneal dialysis do not enhance elimination.
    Supplemental dose is not necessary.",
    " </p>",
    " </div>",
    " <div class=\"block doh drugH1Div\" id=\"F134004\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Hepatic Impairment",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Hypertension: Administer 2.5 mg once daily",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Angina: Administer 5 mg once daily",
    " </p>",
    " </div>",
    " <div class=\"block foc drugH1Div\" id=\"F133971\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosage Forms: U.S.",
    " </span>",
    " <p style=\"text-indent:0em;text-align:justify;display:inline\">",
    " Excipient information presented when available (limited, particularly for
    generics); consult specific product labeling.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Tablet, oral: 2.5 mg, 5 mg, 10 mg",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Norvasc&reg;: 2.5 mg, 5 mg, 10 mg",
    " </p>",
    " </div>",
    " <div class=\"block geq drugH1Div\" id=\"F133957\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Generic Equivalent Available: U.S.",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Yes",
    " </p>",
    " </div>",
    " <div class=\"block adm drugH1Div\" id=\"F133975\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Administration",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " May be administered without regard to meals.",
    " </p>",
    " </div>",
    " <div class=\"block use drugH1Div\" id=\"F133974\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Use",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Treatment of hypertension; treatment of symptomatic chronic stable angina,
    vasospastic (Prinzmetal's) angina (confirmed or suspected); prevention of
    hospitalization due to angina with documented CAD (limited to patients without
    heart failure or ejection fraction &lt;40%)",
    " </p>",
    " </div>",
    " <div class=\"block mst drugH1Div\" id=\"F134051\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Medication Safety Issues",
    " </span>",
    " <div class=\"collapsible\">",
    " <span class=\"collapsible-title\">",
    " Sound-alike/look-alike issues:",
    " </span>",
    " <div class=\"collapsible-wrap\">",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " AmLODIPine may be confused with aMILoride",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Norvasc&reg; may be confused with Navane&reg;, Norvir&reg;, Vascor&reg;",
    " </p>",
    " </div>",
    " </div>",
    " <div class=\"collapsible\">",
    " <span class=\"collapsible-title\">",
    " International issues:",
    " </span>",
    " <div class=\"collapsible-wrap\">",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " Norvasc [U.S., Canada, and multiple international markets] may be confused
    with Vascor brand name for imidapril [Philippines] and simvastatin [Malaysia,
    Singapore, and Thailand]",
    " </p>",
    " </div>",
    " </div>",
    " </div>",
    " <div class=\"block ars drugH1Div\" id=\"F134041\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Adverse Reactions Significant",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " &gt;10%:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Cardiovascular: Peripheral edema (2% to 11% dose related; female 15%; male
    6%; HF patients 27% [Packer, 1996])",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Respiratory: Pulmonary edema (HF patients 27% [Packer, 1996])",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " 1% to 10%:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Cardiovascular: Palpitations (1% to 5% dose related), flushing (1% to 3% dose
    related, more frequent in females)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Central nervous system: Fatigue (5%), dizziness (1% to 3% dose related),
    somnolence (1%)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Dermatologic: Pruritus (1% to 2%), rash (1% to 2%)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Endocrine &amp; metabolic: Male sexual dysfunction (1% to 2%)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Gastrointestinal: Nausea (3%), abdominal pain (2%)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Neuromuscular &amp; skeletal: Muscle cramps (1% to 2%), weakness (1% to 2%)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Respiratory: Dyspnea (1% to 2%)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " &lt;1% (Limited to important or life-threatening): Acute interstitial
    nephritis, allergic reactions, angioedema, anorexia, arrhythmia, arthrosis, atrial
    fibrillation, bradycardia, cholestasis, conjunctivitis, depersonalization,
    depression, diarrhea, diplopia, dysphagia, epistaxis, erythema multiforme,
    exfoliative dermatitis, eye pain, female sexual dysfunction, gingival hyperplasia,
    gynecomastia, hepatitis, hot flushes, hyperglycemia, hypoesthesia, insomnia,
    jaundice, leukocytoclastic vasculitis, leukopenia, micturition disorder,
    micturition frequency, myalgia, nocturia, nonthrombocytopenic purpura, orthostatic
    hypotension, pain, pancreatitis, paresthesia, peripheral ischemia, peripheral
    neuropathy, phototoxicity, purpura, rash erythematous, rash maculopapular, rigors,
    Stevens-Johnson syndrome, syncope, tachycardia, thirst, thrombocytopenia,
    transaminases increased, tremor, vasculitis, ventricular tachycardia, weight
    gain/loss",
    " </p>",
    " </div>",
    " <div class=\"block coi drugH1Div\" id=\"F133979\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Contraindications",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Hypersensitivity to amlodipine or any component of the formulation",
    " </p>",
    " </div>",
    " <div class=\"block war drugH1Div\" id=\"F133961\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Warnings/Precautions",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " <i>",
    " Concerns related to adverse effects:",
    " </i>",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Angina/MI: Increased angina and/or MI have occurred with initiation or
    dosage titration of dihydropyridine calcium channel blockers. Reflex tachycardia
    may occur resulting in angina and/or MI in patients with obstructive coronary
    disease, especially in the absence of concurrent beta-blockade.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Hypotension/syncope: Symptomatic hypotension with or without syncope
    can rarely occur; blood pressure must be lowered at a rate appropriate for the
    patient's clinical condition.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Peripheral edema: The most common side effect is peripheral edema;
    occurs within 2-3 weeks of starting therapy.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " <i>",
    " Disease-related concerns:",
    " </i>",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Aortic stenosis: Use amlodipine with extreme caution in patients with
    severe aortic stenosis; may reduce coronary perfusion resulting in ischemia.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Hepatic impairment: Use with caution in patients with hepatic
    impairment; may require lower starting dose; titrate slowly in patients with severe
    hepatic impairment.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Hypertrophic cardiomyopathy (HCM) with outflow tract obstruction: Use
    amlodipine with caution in patients with HCM and outflow tract obstruction since
    reduction in afterload may worsen symptoms associated with this condition.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " <i>",
    " Special populations:",
    " </i>",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Elderly: Initiate at a lower dose in the elderly.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " <i>",
    " Other warnings/precautions:",
    " </i>",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Titration: Peak antihypertensive effect is delayed; dosage titration
    should occur after 7-14 days on a given dose.",
    " </p>",
    " </div>",
    " <div class=\"block cyt drugH1Div\" id=\"F134037\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Metabolism/Transport Effects",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " <b>",
    " Substrate",
    " </b>",
    " of CYP3A4 (major);",
    " <b>",
    " Note:",
    " </b>",
    " Assignment of Major/Minor substrate status based on clinically relevant drug
    interaction potential;",
    " <b>",
    " Inhibits",
    " </b>",
    " CYP1A2 (moderate), CYP2A6 (weak), CYP2B6 (weak), CYP2C8 (weak), CYP2C9
    (weak), CYP2D6 (weak), CYP3A4 (weak)",
    " </p>",
    " </div>",
    " <div class=\"block dri drugH1Div\" id=\"F133966\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Drug Interactions",
    " </span>",
    " <br/>",
    " <br/>",
    " <div class=\"lexi\" id=\"lexiInteractAddInfo\">",
    " (For additional information:",
    " <a class=\"dip\" href=\"./drug-interaction\" target=\"_blank\">",
    " Launch Lexi-Interact&trade; Drug Interactions Program",
    " </a>",
    " )",
    " </div>",
    " <div class=\"lexi\" id=\"lexiInteractImgB\">",
    " <img border=\"0\" height=\"17\"
    src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\" width=\"71\"/>",
    " </div>",
    " <div class=\"clear\">",
    " </div>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Alpha1-Blockers: May enhance the hypotensive effect of Calcium Channel
    Blockers.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Amifostine: Antihypertensives may enhance the hypotensive effect of
    Amifostine. Management: When amifostine is used at chemotherapy doses,
    antihypertensive medications should be withheld for 24 hours prior to amifostine
    administration. If antihypertensive therapy can not be withheld, amifostine should
    not be administered.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Antifungal Agents (Azole Derivatives, Systemic): May enhance the
    adverse/toxic effect of Calcium Channel Blockers. Specifically, itraconazole may
    enhance the negative inotropic effects of verapamil or diltiazem. Antifungal Agents
    (Azole Derivatives, Systemic) may decrease the metabolism of Calcium Channel
    Blockers. Management: Concurrent use of felodipine or nisoldipine with itraconazole
    is specifically contraindicated. Frequent monitoring is warranted with any such
    combination; calcium channel blocker dose reductions may be required.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Antihypertensives: May enhance the hypotensive effect of other
    Antihypertensives.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration
    of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic
    effects. Aripiprazole dose adjustments may or may not be required based on
    concomitant therapy and/or indication. Consult full interaction monograph for
    specific recommendations.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " ARIPiprazole: CYP2D6 Inhibitors (Weak) may increase the serum concentration
    of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic
    effects. Aripiprazole dose adjustments may or may not be required based on
    concomitant therapy and/or indication. Consult full interaction monograph for
    specific recommendations.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Atosiban: Calcium Channel Blockers may enhance the adverse/toxic effect of
    Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or
    dyspnea.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Barbiturates: May increase the metabolism of Calcium Channel Blockers.
    Management: Monitor for decreased therapeutic effects of calcium channel blockers
    with concomitant barbiturate therapy. Calcium channel blocker dose adjustments may
    be necessary. Nimodipine Canadian labeling contraindicates concomitant use with
    phenobarbital.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Beta-Blockers: Calcium Channel Blockers (Dihydropyridine) may enhance the
    hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have
    also been reported.",
    " <b>",
    " Exceptions:",
    " </b>",
    " Levobunolol; Metipranolol.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Calcium Channel Blockers (Nondihydropyridine): Calcium Channel Blockers
    (Dihydropyridine) may enhance the hypotensive effect of Calcium Channel Blockers
    (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may increase
    the serum concentration of Calcium Channel Blockers (Dihydropyridine).",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Calcium Salts: May diminish the therapeutic effect of Calcium Channel
    Blockers.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " CarBAMazepine: May increase the metabolism of Calcium Channel Blockers
    (Dihydropyridine). Management: Consider calcium channel blocker (CCB) dose
    adjustments or alternative therapy in patients receiving concomitant
    carbamazepine. Nimodipine Canadian labeling contraindicates concurrent use with
    carbamazepine.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of
    Clopidogrel.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Conivaptan: May increase the serum concentration of CYP3A4 Substrates.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " CycloSPORINE (Systemic): May decrease the metabolism of Calcium Channel
    Blockers (Dihydropyridine).",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " CYP1A2 Substrates: CYP1A2 Inhibitors (Moderate) may decrease the metabolism
    of CYP1A2 Substrates.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates.
    Management: Consider an alternative for one of the interacting drugs. Some
    combinations may be specifically contraindicated. Consult appropriate manufacturer
    labeling.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4
    Substrates.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4
    Substrates.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Dasatinib: May increase the serum concentration of CYP3A4 Substrates.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Deferasirox: May decrease the serum concentration of CYP3A4 Substrates.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Diazoxide: May enhance the hypotensive effect of Antihypertensives.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Fluconazole: May decrease the metabolism of Calcium Channel Blockers.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Fosphenytoin: Calcium Channel Blockers may increase the serum concentration
    of Fosphenytoin. Management: Monitor for phenytoin toxicity with concomitant use
    of a calcium channel blocker (CCB) or decreased phenytoin effects with CCB
    discontinuation. Monitor for decreased CCB therapeutic effects. Nimodipine Canadian
    labeling contraindicates use with phenytoin.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Grapefruit Juice: May increase the serum concentration of AmLODIPine.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates.
    Management: Consider avoiding CYP3A4 inducing herbs in order to avoid therapeutic
    failure of the substrate. Some combinations may be specifically contraindicated.
    Consult appropriate manufacturer labeling.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Herbs (Hypertensive Properties): May diminish the antihypertensive effect of
    Antihypertensives.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Herbs (Hypotensive Properties): May enhance the hypotensive effect of
    Antihypertensives.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive
    Agents.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Ivacaftor: May increase the serum concentration of CYP3A4 Substrates.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of
    Lomitapide. Management: Limit the maximum adult dose of lomitapide to 30 mg daily
    when used in combination with any weak CYP3A4 inhibitor.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Macrolide Antibiotics: May decrease the metabolism of Calcium Channel
    Blockers. Management: Consider using a noninteracting macrolide. Monitor for
    increased therapeutic effects of calcium channel blockers if an interacting
    macrolide antibiotic is initiated, or decreased effects if a macrolide is
    discontinued.",
    " <b>",
    " Exceptions:",
    " </b>",
    " Azithromycin (Systemic); Fidaxomicin; Spiramycin.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Magnesium Salts: Calcium Channel Blockers may enhance the adverse/toxic
    effect of Magnesium Salts. Magnesium Salts may enhance the hypotensive effect of
    Calcium Channel Blockers.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " MAO Inhibitors: May enhance the hypotensive effect of Antihypertensives. MAO
    Inhibitors may enhance the orthostatic hypotensive effect of Antihypertensives.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Melatonin: May diminish the antihypertensive effect of Calcium Channel
    Blockers (Dihydropyridine).",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Methylphenidate: May diminish the antihypertensive effect of
    Antihypertensives.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Mifepristone: May increase the serum concentration of CYP3A4 Substrates.
    Management: Minimize doses of CYP3A4 substrates, and monitor for increased
    concentrations/toxicity, during and 2 weeks following treatment with mifepristone.
    Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine,
    sirolimus, and tacrolimus.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Nafcillin: May increase the metabolism of Calcium Channel Blockers.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may
    enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents
    (Nondepolarizing).",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Nitroprusside: Calcium Channel Blockers may enhance the hypotensive effect of
    Nitroprusside.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Pentoxifylline: May enhance the hypotensive effect of Antihypertensives.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Phenytoin: Calcium Channel Blockers may increase the serum concentration of
    Phenytoin. Management: Monitor for phenytoin toxicity with concomitant use of a
    calcium channel blocker (CCB) or decreased phenytoin effects with CCB
    discontinuation. Monitor for decreased CCB therapeutic effects. Nimodipine Canadian
    labeling contraindicates use with phenytoin.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of
    Antihypertensives.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of
    Pimozide.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Pirfenidone: CYP1A2 Inhibitors (Moderate) may increase the serum
    concentration of Pirfenidone. Management: This combination may be used with
    caution only if the moderate CYP1A2 inhibitor does not significantly inhibit other
    CYP enzymes and the patient is not taking any other drugs that do significantly
    inhibit other specific CYP enzymes.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Prostacyclin Analogues: May enhance the hypotensive effect of
    Antihypertensives.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Protease Inhibitors: May decrease the metabolism of Calcium Channel Blockers
    (Dihydropyridine).",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " QuiNIDine: May increase the serum concentration of Calcium Channel Blockers
    (Dihydropyridine). Calcium Channel Blockers (Dihydropyridine) may decrease the
    serum concentration of QuiNIDine. Calcium Channel Blockers (Dihydropyridine) may
    increase the serum concentration of QuiNIDine.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Rifamycin Derivatives: May increase the metabolism of Calcium Channel
    Blockers. This primarily affects oral forms of calcium channel blockers.
    Management: The labeling for some U.S. and Canadian calcium channel blockers
    contraindicate use with rifampin however recommendations vary. Consult appropriate
    labeling.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " RiTUXimab: Antihypertensives may enhance the hypotensive effect of
    RiTUXimab.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Simvastatin: AmLODIPine may increase the serum concentration of Simvastatin.
    Management: Avoid the concurrent use of amlodipine with simvastatin when possible.
    If used together, avoid doses of simvastatin greater than 20 mg/day (for adults).",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Tacrolimus (Systemic): Calcium Channel Blockers (Dihydropyridine) may
    increase the serum concentration of Tacrolimus (Systemic).",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Yohimbine: May diminish the antihypertensive effect of Antihypertensives.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " </div>",
    " <div class=\"block foi drugH1Div\" id=\"F133994\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Ethanol/Nutrition/Herb Interactions",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Food: Grapefruit juice may modestly increase amlodipine levels.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Herb/Nutraceutical: St John's wort may decrease amlodipine levels. Avoid
    herbs with",
    " <i>",
    " hypertensive",
    " </i>",
    " properties (bayberry, blue cohosh, cayenne, ephedra, ginger, ginseng
    [American], kola, licorice). Avoid herbs with",
    " <i>",
    " hypotensive",
    " </i>",
    " properties (black cohosh, California poppy, coleus, garlic, goldenseal,
    hawthorn, mistletoe, periwinkle, quinine, shepherd's purse).",
    " </p>",
    " </div>",
    " <div class=\"block prf drugH1Div\" id=\"F133968\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pregnancy Risk Factor",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " C (",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?16/42/17068\">",
    " show table",
    " </a>",
    " )",
    " </p>",
    " </div>",
    " <div class=\"block pri drugH1Div\" id=\"F133982\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pregnancy Implications",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Embryotoxic effects have been demonstrated in animal studies. No well-
    controlled studies have been conducted in pregnant women. Use in pregnancy only
    when clearly needed and when the benefits outweigh the potential hazard to the
    fetus.",
    " </p>",
    " </div>",
    " <div class=\"block lac drugH1Div\" id=\"F134007\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Lactation",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Excretion in breast milk unknown/not recommended",
    " </p>",
    " </div>",
    " <div class=\"block dic drugH1Div\" id=\"F133983\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dietary Considerations",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " May be taken without regard to meals.",
    " </p>",
    " </div>",
    " <div class=\"block fee drugH1Div\" id=\"F133981\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pricing: U.S. (Medi-Span&reg;)",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Tablets",
    " </b>",
    " (AmLODIPine Besylate Oral)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " 2.5 mg (90): $155.66",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " 5 mg (90): $155.68",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " 10 mg (90): $213.65",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Tablets",
    " </b>",
    " (Norvasc Oral)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " 2.5 mg (90): $292.36",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " 5 mg (100): $324.84",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " 10 mg (90): $400.84",
    " </p>",
    " </div>",
    " <div class=\"block mop drugH1Div\" id=\"F5085856\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Monitoring Parameters",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Heart rate, blood pressure, peripheral edema",
    " </p>",
    " </div>",
    " <div class=\"list fbnlist drugH1Div drugBrandNames\" id=\"F133984\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " International Brand Names",
    " </span>",
    " <ul>",
    " <li>",
    " A-B Vask (ID);",
    " </li>",
    " <li>",
    " Actapin (HK, ID, SG);",
    " </li>",
    " <li>",
    " Aforbes (PH);",
    " </li>",
    " <li>",
    " Agen (EE);",
    " </li>",
    " <li>",
    " Alopine (TW);",
    " </li>",
    " <li>",
    " Amaday (PH);",
    " </li>",
    " <li>",
    " Ambesyl (PH);",
    " </li>",
    " <li>",
    " Amcal (PH);",
    " </li>",
    " <li>",
    " Amcard (IN);",
    " </li>",
    " <li>",
    " Amcardia (TH);",
    " </li>",
    " <li>",
    " Amdepin (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC,
    SD, SL, SN, TN, TZ, UG, ZM, ZW);",
    " </li>",
    " <li>",
    " Amdipin (CO, PE);",
    " </li>",
    " <li>",
    " Amdixal (ID);",
    " </li>",
    " <li>",
    " Amedin (HK);",
    " </li>",
    " <li>",
    " Amilo (TW);",
    " </li>",
    " <li>",
    " Amlate (ZA);",
    " </li>",
    " <li>",
    " Amlibon (MY);",
    " </li>",
    " <li>",
    " Amlo-M (KP);",
    " </li>",
    " <li>",
    " Amloc (AR, CN);",
    " </li>",
    " <li>",
    " Amlocar (PE);",
    " </li>",
    " <li>",
    " Amlod (HK, TH);",
    " </li>",
    " <li>",
    " Amlodac (MY, TW);",
    " </li>",
    " <li>",
    " Amlodigamma (HK);",
    " </li>",
    " <li>",
    " Amlodin (JP);",
    " </li>",
    " <li>",
    " Amlodine (PH, TW);",
    " </li>",
    " <li>",
    " Amlong (HK, MY, SG);",
    " </li>",
    " <li>",
    " Amlopin (HR, KP, PL);",
    " </li>",
    " <li>",
    " Amlopine (TH);",
    " </li>",
    " <li>",
    " Amlopres (HK);",
    " </li>",
    " <li>",
    " Amlor (BE, FR, IL, LU);",
    " </li>",
    " <li>",
    " Amlostar (KP);",
    " </li>",
    " <li>",
    " Amlosyn (CO);",
    " </li>",
    " <li>",
    " Amlotens (SG);",
    " </li>",
    " <li>",
    " Amlovas (CR, DO, GT, HN, NI, PA, SV);",
    " </li>",
    " <li>",
    " Amlovasc (CH);",
    " </li>",
    " <li>",
    " Amlozen (HK);",
    " </li>",
    " <li>",
    " Amodin (KP);",
    " </li>",
    " <li>",
    " Amodipin (KP);",
    " </li>",
    " <li>",
    " Ampliron (PY);",
    " </li>",
    " <li>",
    " Amtas (SG);",
    " </li>",
    " <li>",
    " Amze (AR);",
    " </li>",
    " <li>",
    " Anoldin (MY);",
    " </li>",
    " <li>",
    " Anydipine (KP);",
    " </li>",
    " <li>",
    " Astudal (ES);",
    " </li>",
    " <li>",
    " Avevasc (MY, SG);",
    " </li>",
    " <li>",
    " Avistar (MX);",
    " </li>",
    " <li>",
    " Bezam (PH);",
    " </li>",
    " <li>",
    " Calbivas (ID);",
    " </li>",
    " <li>",
    " Calbloc (PH);",
    " </li>",
    " <li>",
    " Calchek (IN);",
    " </li>",
    " <li>",
    " Calvase (NZ);",
    " </li>",
    " <li>",
    " Cardol (PH);",
    " </li>",
    " <li>",
    " Cobisk (KP);",
    " </li>",
    " <li>",
    " Comdipin (ID);",
    " </li>",
    " <li>",
    " Cordarene (BR);",
    " </li>",
    " <li>",
    " Covasc (MY);",
    " </li>",
    " <li>",
    " CP-Lovac (HK);",
    " </li>",
    " <li>",
    " DAILYvasc (PH);",
    " </li>",
    " <li>",
    " Derox-5 (PH);",
    " </li>",
    " <li>",
    " Deten (TH);",
    " </li>",
    " <li>",
    " Du.Q (TW);",
    " </li>",
    " <li>",
    " Duactin 5 (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE);",
    " </li>",
    " <li>",
    " Ertensi (ID);",
    " </li>",
    " <li>",
    " Fulopin (ID);",
    " </li>",
    " <li>",
    " Gensia (ID);",
    " </li>",
    " <li>",
    " Gravask (ID);",
    " </li>",
    " <li>",
    " Hovasc (HK, MY);",
    " </li>",
    " <li>",
    " Istin (GB, IE);",
    " </li>",
    " <li>",
    " Lama (IN);",
    " </li>",
    " <li>",
    " Lofral (HK, MY);",
    " </li>",
    " <li>",
    " Lovas (TH);",
    " </li>",
    " <li>",
    " Lowdipine (KP);",
    " </li>",
    " <li>",
    " Narvin (TH);",
    " </li>",
    " <li>",
    " Nor-Lodipina (DO, GT, HN, NI, SV);",
    " </li>",
    " <li>",
    " Nordipine (MY);",
    " </li>",
    " <li>",
    " Normodipine (HU, SG);",
    " </li>",
    " <li>",
    " Norvas (CO, ES, MX);",
    " </li>",
    " <li>",
    " Norvasc (AT, AU, BB, BF, BG, BJ, BM, BR, BS, BZ, CH, CI, CL, CN, CR, CZ, DE,
    DK, DO, EC, EE, ET, FI, GH, GM, GN, GR, GT, GY, HK, HN, HU, IL, IT, JM, JP, KE, KP,
    LR, MA, ML, MR, MU, MW, MY, NE, NG, NI, NL, NO, NZ, PA, PE, PH, PK, PT, RU, SC, SD,
    SE, SG, SL, SN, SR, SV, TH, TN, TR, TT, TW, TZ, UG, UY, VE, ZA, ZM, ZW);",
    " </li>",
    " <li>",
    " Norvask (ID);",
    " </li>",
    " <li>",
    " Novaspin (KP);",
    " </li>",
    " <li>",
    " Odasyl (PH);",
    " </li>",
    " <li>",
    " Ozlodip (AU);",
    " </li>",
    " <li>",
    " Perivasc (AU);",
    " </li>",
    " <li>",
    " Presilam (CN);",
    " </li>",
    " <li>",
    " Provasc (PH);",
    " </li>",
    " <li>",
    " Rustin (IE);",
    " </li>",
    " <li>",
    " Sinnorvapin (KP);",
    " </li>",
    " <li>",
    " Sinop (AR);",
    " </li>",
    " <li>",
    " Sistopress (MX);",
    " </li>",
    " <li>",
    " Stadovas (HK);",
    " </li>",
    " <li>",
    " Stamlo (SG);",
    " </li>",
    " <li>",
    " Tensivask (ID);",
    " </li>",
    " <li>",
    " Vasotop (EC);",
    " </li>",
    " <li>",
    " Vasten (CO);",
    " </li>",
    " <li>",
    " Zynor (HK, MY)",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"block pha drugH1Div\" id=\"F133960\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Mechanism of Action",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Inhibits calcium ion from entering the &ldquo;slow channels&rdquo; or select
    voltage-sensitive areas of vascular smooth muscle and myocardium during
    depolarization, producing a relaxation of coronary vascular smooth muscle and
    coronary vasodilation; increases myocardial oxygen delivery in patients with
    vasospastic angina. Amlodipine directly acts on vascular smooth muscle to produce
    peripheral arterial vasodilation reducing peripheral vascular resistance and blood
    pressure.",
    " </p>",
    " </div>",
    " <div class=\"block phk drugH1Div\" id=\"F133978\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pharmacodynamics/Kinetics",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Duration of antihypertensive effect: 24 hours",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Absorption: Oral: Well absorbed",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Distribution: V",
    " <sub>",
    " d",
    " </sub>",
    " : 21 L/kg",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Protein binding: 93% to 98%",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Metabolism: Hepatic (&gt;90%) to inactive metabolites",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Bioavailability: 64% to 90%",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Half-life elimination: Terminal: 30-50 hours; increased with hepatic
    dysfunction",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Time to peak, plasma: 6-12 hours",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Excretion: Urine (10% of total dose as unchanged drug, 60% of total dose as
    metabolites)",
    " </p>",
    " </div>",
    " </div>",
    " <div id=\"topicAgreement\">",
    " Use of UpToDate is subject to the",
    " <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
    target=\"_blank\">",
    " Subscription and License Agreement",
    " </a>",
    " .",
    " </div>",
    " <div class=\"headingAnchor\" id=\"references\">",
    " <h1>",
    " REFERENCES",
    " </h1>",
    " <ol id=\"reference\">",
    " <li>",
    " <div class=\"reference\">",
    " ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research
    Group, \"Major Outcomes in High-Risk Hypertensive Patients Randomized to
    Angiotensin-Converting Enzyme Inhibitor or Calcium Channel Blocker vs Diuretic: The
    Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial
    (ALLHAT),\"",
    " <i>",
    " JAMA",
    " </i>",
    " , 2002, 288(23):2981-97.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?0/18/296/abstract-text/12479763/pubmed\" id=\"12479763\"
    target=\"_blank\">",
    " 12479763",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Aronow WS, Fleg JL, Pepine CJ, et al, &ldquo;ACCF/AHA 2011 Expert Consensus
    Document on Hypertension in the Elderly: A Report of the American College of
    Cardiology Foundation Task Force on Clinical Expert Consensus Documents,&rdquo;",
    " <i>",
    " Circulation",
    " </i>",
    " , 2011, 123(21):2434-506.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?0/18/296/abstract-text/21518977/pubmed\" id=\"21518977\"
    target=\"_blank\">",
    " 21518977",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Braunwald E, Antman EM, Beasley JW, et al, &ldquo;ACC/AHA Guidelines for the
    Management of Patients With Unstable Angina and Non-ST-Segment Elevation Myocardial
    Infarction. A Report of the American College of Cardiology/American Heart
    Association Task Force on Practice Guidelines (Committee on the Management of
    Patients With Unstable Angina),&rdquo;",
    " <i>",
    " J Am Coll Cardiol",
    " </i>",
    " , 2000, 36(3):970-1062.",
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    " </ol>",
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    " REFERENCES",
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    var title_f0_18_297="High altitude illness: Physiology, risk factors, and general
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    " High altitude illness: Physiology, risk factors, and general prevention",
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    " Oct 18, 2012.",
    " </div>",
    " <div id=\"topicText\">",
    " <p class=\"headingAnchor\" id=\"H1\">",
    " <span class=\"h1\">",
    " INTRODUCTION",
    " </span>",
    " &nbsp;&mdash;&nbsp;Every year the beauty and recreational opportunities of the
    mountains attract millions of visitors from lowland elevations to high-altitude
    destinations worldwide. Resort towns in the Western United States alone attract
    over 30 million visitors annually, generally to sleeping elevations in the 2000 to
    3000 m (6500 to 9800 ft) range. Many more millions visit cities at these
    elevations, including several large cities in South America and Asia situated above
    3000 m [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/1\">",
    " 1",
    " </a>",
    " ]. Most of these destinations can be reached within a day using modern means
    of transportation.",
    " </p>",
    " <p>",
    " In addition, tens of thousands of climbers, trekkers, and skiers worldwide
    ascend to elevations in the 3000 to 5500 m (9800 to 18,000 ft) range, often at a
    rate that exceeds an individual's ability to acclimatize. An ever-growing number of
    mountaineers seek the summits of peaks over 5500 m. Military, rescue, and other
    professional personnel may also be called upon to ascend to high altitudes with
    little or no time for acclimatization. Such rapid ascents place the unacclimatized
    traveler at risk for developing high altitude illness (HAI).",
    " </p>",
    " <p>",
    " Clinicians working in or near mountainous areas must familiarize themselves
    with the presentation and management of HAI, while all health care workers who
    advise travelers need to understand the best prevention strategies and treatment
    options. The different types of HAI, their pathophysiology, and methods for
    prevention will be reviewed here. The diagnosis and treatment of specific types of
    HAI are discussed separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?1/6/1130?
    source=see_link\">",
    " \"Acute mountain sickness and high altitude cerebral edema\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?28/16/28936?
    source=see_link\">",
    " \"High altitude pulmonary edema\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?15/42/16042?
    source=see_link\">",
    " \"High altitude, air travel, and heart disease\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H2\">",
    " <span class=\"h1\">",
    " HIGH ALTITUDE PHYSIOLOGY",
    " </span>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H3\">",
    " <span class=\"h2\">",
    " Hypobaric hypoxia",
    " </span>",
    " &nbsp;&mdash;&nbsp;The partial pressure of oxygen (PO2) is the driving force
    for the diffusion of oxygen molecules down the oxygen cascade: from inspired air to
    alveolar air, then into the blood, and ultimately into the cells and mitochondria.
    The partial pressure of oxygen of inspired air (PIO2) is given by the equation:
    PIO2 = FIO2 x (Pb - 47 mmHg), where FIO2 is the fraction of oxygen in inspired air,
    Pb is the barometric pressure, and 47 mmHg is the vapor pressure of H2O at
    37&deg;C.",
    " </p>",
    " <p>",
    " The proportion of air comprised by oxygen (FIO2, 20.94 percent) remains
    constant at the highest terrestrial elevations and even into the upper troposphere.
    The alveolar vapor pressure of water is also constant at 47 mmHg. Hence, the PIO2
    and therefore, the oxygen cascade, are directly affected by barometric pressure.",
    " </p>",
    " <p>",
    " Barometric pressure (Pb) diminishes exponentially with increasing altitude (",
    " <a class=\"graphic graphic_table graphicRef63999 \" href=\"UTD.htm?
    8/24/8588\">",
    " table 1",
    " </a>",
    " and",
    " <a class=\"graphic graphic_table graphicRef50199 \" href=\"UTD.htm?0/4/71\">",
    " table 2",
    " </a>",
    " ). Barometric pressure at altitude also decreases with lower temperature,
    higher latitude, inclement weather, and during winter. Although the effect of these
    variables upon Pb is not nearly as significant as altitude, it becomes
    physiologically significant at elevations over approximately 2800 m (9200 ft) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/2\">",
    " 2",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Diminished PIO2 at altitude is the direct result of lower barometric pressure.
    As PIO2 decreases, so does the partial pressure of alveolar oxygen (PAO2), arterial
    PO2 (PaO2), and arterial oxygen saturation (SpO2), resulting in tissue hypoxia.
    This form of hypoxia is termed hypobaric hypoxia, and it represents the initial
    cause of high altitude illness.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H4\">",
    " <span class=\"h2\">",
    " Acclimatization",
    " </span>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H5\">",
    " <span class=\"h3\">",
    " Overview",
    " </span>",
    " &nbsp;&mdash;&nbsp;As PIO2 decreases with ascent, the normal driving pressure
    of PO2 down the oxygen cascade diminishes, resulting in progressive tissue hypoxia
    (",
    " <a class=\"graphic graphic_figure graphicRef56808 \" href=\"UTD.htm?
    29/55/30590\">",
    " figure 1",
    " </a>",
    " )&nbsp;[",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/1,3,4\">",
    " 1,3,4",
    " </a>",
    " ]. The normal compensatory responses to acute hypobaric hypoxia are termed
    acclimatization, an incompletely understood, complex series of physiologic changes
    involving multiple organ systems that occurs over varying periods (from minutes to
    weeks). Acclimatization reduces the gradient between PIO2 and tissue PO2, thus
    optimizing the delivery and utilization of oxygen at the cellular level.",
    " </p>",
    " <p>",
    " Acclimatization differs from the term adaptation, which refers to physiologic
    changes that take place in response to chronic exposure to hypobaric hypoxia over
    generations and are observed in some populations permanently situated at high
    altitude. The capacity to acclimatize varies greatly among individuals and is
    dependent upon many factors, including the degree of hypoxic stress (rate of
    ascent, altitude attained), the intrinsic capacity of the individual to compensate
    for diminished PaO2 (genetic and anatomic variation, medical conditions), and
    extrinsic factors, which may enhance or interfere with compensatory mechanisms (eg,
    alcohol, medications, temperature) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/5\">",
    " 5",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " The process of acclimatization begins within minutes of ascent, but requires
    several weeks to complete. Hypoxia-inducible factor-1-alpha (HIF-1-a) is a
    transcription factor responsible for activating more than 100 genes in response to
    hypoxia, and its activation initiates acclimatization.",
    " </p>",
    " <p>",
    " Although the complex compensatory changes that occur cannot fully restore
    tissue PO2 to sea-level values, acclimatization can substantially improve oxygen
    delivery and utilization. In fact, acclimatization enables some climbers to
    function with only minor difficulty on the peak of Mount Everest (8848 m or 29,029
    ft) without supplemental oxygen [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/3\">",
    " 3",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " At 8848 m, PIO2 is 43.1 mmHg, equivalent to breathing 6 percent oxygen at sea
    level. Sudden exposure to such high altitude (eg, pilot's cockpit suddenly
    decompresses) results in loss of consciousness and death [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/1\">",
    " 1",
    " </a>",
    " ]. A detailed discussion of acclimatization is beyond the scope of this
    review, but can be found in several excellent sources [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/1,6\">",
    " 1,6",
    " </a>",
    " ]. A brief review of the beneficial changes that occur during acclimatization
    is provided below. Other aspects of respiratory physiology are discussed
    separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?39/4/40008?
    source=see_link\">",
    " \"Control of ventilation\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?8/40/8839?
    source=see_link\">",
    " \"Physiology of dyspnea\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H6\">",
    " <span class=\"h3\">",
    " Ventilation and PaO2",
    " </span>",
    " &nbsp;&mdash;&nbsp;The first and most important step in improving oxygen
    delivery is an increase in ventilation. Without increased ventilation, humans could
    not tolerate altitudes higher than 5000 m (16,400 ft) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/1,3,4\">",
    " 1,3,4",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Hypoxic stimulation of the peripheral chemoreceptors (at the carotid and
    aortic bodies) results in increased minute ventilation and is termed the hypoxic
    ventilatory response (HVR). HVR increases in sensitivity over several days spent at
    altitude. Simultaneously, the PCO2 level at which ventilation is stimulated is
    lowered (hypercapnic ventilatory response (HCVR)), further increasing the
    ventilatory response to high altitude. Overall, minute ventilation increases in a
    nearly linear fashion with diminishing SpO2 and results in reduced alveolar CO2,
    which increases alveolar O2 by reducing the dilutional effect of CO2 in alveolar
    air [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/4\">",
    " 4",
    " </a>",
    " ]. Ventilation reaches a maximum only after four to seven days at the same
    altitude. This hyperventilation results in a respiratory alkalosis.",
    " </p>",
    " <p>",
    " HVR is genetically determined and quite variable among healthy, physically fit
    individuals. In addition, HVR is affected by extrinsic factors, such as respiratory
    depressants (eg, alcohol and",
    " <span class=\"nowrap\">",
    " sedative/hypnotics)",
    " </span>",
    " and fragmented sleep. Conversely, respiratory stimulants (eg, progesterone,
    almitrine) and sympathomimetics (eg, coca, caffeine) increase HVR.",
    " </p>",
    " <p>",
    " While one might assume that a brisk HVR would reduce the degree of hypoxia and
    protect against AMS, studies have failed to demonstrate this finding consistently.
    Some elite climbers, endurance athletes, and high altitude residents (Sherpas and
    Andean peoples) have low HVR and perform well at altitude. However, a low HVR is
    associated with an increased risk of HAPE, perhaps because it augments hypoxia-
    induced pulmonary vasoconstriction, leading to an exaggerated increase in pulmonary
    artery (PA) pressure [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/1,6\">",
    " 1,6",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " As ventilation rises in response to hypoxia, PaCO2 falls and pH rises. The
    central chemoreceptors in the medulla of the brain respond to alkalosis in the
    cerebral spinal fluid (CSF) by inhibiting ventilation, such that the full hypoxic
    ventilatory response is attenuated.",
    " </p>",
    " <p>",
    " Partial renal compensation for respiratory alkalosis occurs within 24 to 48
    hours of ascent as the kidneys excrete bicarbonate, decreasing the pH toward
    normal, and allowing ventilation to again increase as the alkalosis is reduced.
    Plasma bicarbonate concentration continues to drop and ventilation to rise with
    further increases in altitude.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H7\">",
    " <span class=\"h3\">",
    " Circulatory changes",
    " </span>",
    " &nbsp;&mdash;&nbsp;Circulatory changes following ascent involve the systemic,
    pulmonary, and cerebral vasculatures. Following a rapid and sustained increase in
    altitude, increased sympathetic activity transiently increases cardiac output,
    blood pressure, heart rate, and venous tone. Heart rate remains elevated while
    stroke volume is diminished due to decreased plasma volume, which can drop as much
    as 12 percent over the first 24 hours from bicarbonate diuresis, fluid shift from
    the intravascular space, and suppression of aldosterone [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/1\">",
    " 1",
    " </a>",
    " ]. The effects of altitude upon cardiac function are discussed in detail
    separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?15/42/16042?
    source=see_link\">",
    " \"High altitude, air travel, and heart disease\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " The pulmonary vasculature constricts in response to hypoxia, resulting in
    prompt, but highly variable increases in pulmonary vascular resistance and PA
    pressure. Increased flow to usually under-perfused areas may augment gas exchange
    by improving",
    " <span class=\"nowrap\">",
    " ventilation/perfusion",
    " </span>",
    " matching. However, an exaggerated increase in PA pressure and pulmonary
    vascular resistance (PVR) is associated with susceptibility to HAPE, as is markedly
    inconsistent vasoconstriction of pulmonary arterioles. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?28/16/28936?
    source=see_link&amp;anchor=H2#H2\">",
    " \"High altitude pulmonary edema\", section on 'Pathophysiology'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " At altitude, mild pulmonary hypertension at rest can be markedly increased by
    vigorous exercise, with pulmonary pressure reaching near-systemic levels,
    especially in people with a history of HAPE. Cold ambient temperatures at high
    altitude also increase pulmonary artery pressure.",
    " </p>",
    " <p>",
    " In the brain, oxygen delivery is dependent upon cerebral blood flow (CBF),
    which in turn depends upon a balance of vasodilation (in response to hypoxia),
    vasoconstriction (in response to hypocapnia), and changes in autoregulation. While
    there is considerable variation of cerebral autoregulation among hypoxic
    individuals, CBF and oxygen delivery is generally maintained down to SpO2 levels of
    70 to 80 percent despite marked hypocapnia. Individual variation in cerebral blood
    flow is linked to differences in ventilatory responses to hypoxia and hypocapnia.
    Despite mild regional brain tissue hypoxia revealed by near infrared spectroscopy,
    overall global cerebral metabolism is well-maintained during moderate hypoxia [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/7\">",
    " 7",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H8\">",
    " <span class=\"h3\">",
    " Hematologic changes",
    " </span>",
    " &nbsp;&mdash;&nbsp;Increased hemoglobin concentration ([Hb]) is a well known
    component of high altitude acclimatization. A modest increase in [Hb] is beneficial
    by increasing the oxygen-carrying capacity of blood.",
    " </p>",
    " <p>",
    " In the first few days at altitude, [Hb] is increased due to plasma volume
    contraction. Within a few hours, hypoxemia stimulates increased production of
    erythropoietin from specialized renal cells, which increases the production of red
    blood cells (RBCs) over 10 to 14 days, resulting in an increased [Hb]. Up to
    altitudes of approximately 4000 m, this increase is sufficient to balance the
    reduction in oxygen saturation and restore the oxygen content of arterial blood to
    sea level values (though now at a lower PO2).",
    " </p>",
    " <p>",
    " The oxyhemoglobin dissociation curve (ODC) plays a crucial role in oxygen
    transport. Because of the sigmoid shape of the curve, arterial oxygen saturation
    (SpO2) is well-maintained up to 3000 m, despite a significant decrease in arterial
    PO2 (PaO2). Above that altitude, small changes in PaO2 result in large changes in
    SpO2. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?22/29/23001?
    source=see_link\">",
    " \"Structure and function of normal human hemoglobins\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " While SpO2 determines arterial oxygen transport, PaO2 determines diffusion of
    oxygen from the capillary to the cell. Intraerythrocytic alkalosis causes a
    leftward shift of the ODC, but alkalosis is a major stimulus for the production of
    2,3 DPG, which shifts the ODC back toward its normal position. This balance between
    alkalosis (left shift) and increased 2,3 DPG (right shift) is maintained until
    sojourners reach very high altitudes. There, the effect of the alkalosis far
    outstrips the capacity of the RBC to produce more 2,3 DPG, leading to a leftward
    shift of the ODC.",
    " </p>",
    " <p>",
    " As an example, in climbers at the summit of Mt. Everest the PaCO2 is 8 to 10
    mmHg and the pH rises above 7.6. The resulting shift of the ODC to the left
    facilitates oxygen-hemoglobin binding in the lung, which results in an advantageous
    rise in SpO2. Also, animals adapted to high altitude (eg, yaks, llamas, bar-headed
    geese) have left-shifted ODCs compared with their low-altitude counterparts.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H9\">",
    " <span class=\"h3\">",
    " Oxygen delivery and utilization",
    " </span>",
    " &nbsp;&mdash;&nbsp;Diffusion of oxygen from the capillaries to the
    mitochondria and its subsequent utilization by these organelles, constitutes the
    final link of the oxygen cascade.",
    " </p>",
    " <p>",
    " Diffusion distance from capillary wall to mitochondria is decreased at high
    altitude, mainly because of reduction in the diameter of muscle fibers, which
    atrophy during high altitude expeditions. This atrophy occurs due to a net energy
    deficit and deconditioning effect [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/8\">",
    " 8",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " At the tissue level, HIF-1-a stimulates vascular endothelial growth factor
    (VEGF), which stimulates angiogenesis and nitric oxide synthesis. This results in
    greater blood flow and oxygen delivery to tissues. Improvements in oxidative
    metabolism and tissue gas exchange also occur.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H10\">",
    " <span class=\"h1\">",
    " DEFINITIONS",
    " </span>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H11\">",
    " <span class=\"h2\">",
    " High altitude illness",
    " </span>",
    " &nbsp;&mdash;&nbsp;High altitude illness (HAI) is the collective term for the
    unique cerebral and pulmonary syndromes that can occur following an initial ascent
    to high altitude or following a further ascent while already at high altitude. HAI
    includes acute mountain sickness (AMS) and high altitude cerebral edema (HACE),
    which afflict the brain, and high altitude pulmonary edema (HAPE), which afflicts
    the lungs. They are induced by the hypoxic stress of high altitude and are
    characterized by extravascular fluid accumulation in the brain (AMS and HACE) and
    lungs (HAPE). All respond to descent and oxygen therapy.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H12\">",
    " <span class=\"h2\">",
    " Acute mountain sickness and high altitude cerebral edema",
    " </span>",
    " &nbsp;&mdash;&nbsp;Most experts consider acute mountain sickness (AMS) and
    high altitude cerebral edema (HACE) to represent different points of severity along
    the same pathophysiologic process in the brain. This process may collectively be
    referred to as",
    " <span class=\"nowrap\">",
    " AMS/HACE.",
    " </span>",
    " </p>",
    " <p>",
    " AMS",
    " is the most common form of high altitude illness and may occur following rapid
    ascent [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/1,5,6,9\">",
    " 1,5,6,9",
    " </a>",
    " ]. It is characterized by headache in combination with other nonspecific
    symptoms, such as malaise and anorexia.",
    " </p>",
    " <p>",
    " HACE is the least common form of high altitude illness, but is rapidly fatal
    without prompt recognition and treatment. AMS and HACE are discussed in detail
    separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?1/6/1130?
    source=see_link\">",
    " \"Acute mountain sickness and high altitude cerebral edema\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H13\">",
    " <span class=\"h2\">",
    " High altitude pulmonary edema",
    " </span>",
    " &nbsp;&mdash;&nbsp;High altitude pulmonary edema (HAPE) is an uncommon, life-
    threatening noncardiogenic pulmonary edema that develops two to four days following
    rapid ascent above 2500 m (8000 ft) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/10\">",
    " 10",
    " </a>",
    " ]. HAPE, which may accompany",
    " <span class=\"nowrap\">",
    " AMS/HACE,",
    " </span>",
    " is the most common cause of death among the high altitude illnesses. HAPE is
    discussed in detail separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?28/16/28936?
    source=see_link\">",
    " \"High altitude pulmonary edema\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H14\">",
    " <span class=\"h2\">",
    " Other altitude-related illnesses",
    " </span>",
    " &nbsp;&mdash;&nbsp;Altered breathing with non-REM sleep, a phenomenon known as
    periodic breathing of altitude, is encountered at altitudes over 2500 m and becomes
    very common at higher altitudes [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/11-13\">",
    " 11-13",
    " </a>",
    " ]. It is a form of Cheyne-Stokes respiration and reflects changes in neural
    signaling due to hypoxia (respiratory stimulant) and alkalosis (respiratory
    depressant) during sleep. Periodic breathing of altitude may occur at altitudes as
    low as 1400 m, but generally does not disrupt sleep until climbers reach altitudes
    above 3500 m. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?21/63/22520?
    source=see_link\">",
    " \"Disorders of ventilatory control\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " High altitude retinal hemorrhage occurs when there is rupture of retinal
    arterioles leading to extravasation of blood into the retina [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/14-16\">",
    " 14-16",
    " </a>",
    " ]. The retinal circulation develops many of the same changes seen in the
    cerebral circulation at altitude. It is most common at elevations above 5000 m
    (16,400 ft), particularly among those engaged in strenuous activity. Symptoms
    rarely develop unless hemorrhage extends to the macula.",
    " </p>",
    " <p>",
    " Numerous medical illnesses other than",
    " <span class=\"nowrap\">",
    " AMS/HACE",
    " </span>",
    " and HAPE may be caused or exacerbated by high altitude (",
    " <a class=\"graphic graphic_table graphicRef75758 \" href=\"UTD.htm?
    40/28/41420\">",
    " table 3",
    " </a>",
    " ). Examples include: problems resulting from chronic altitude exposure, such
    as chronic mountain sickness and high altitude pulmonary hypertension; preexisting
    medical conditions exacerbated by hypoxia, such as ischemic heart disease; and
    conditions arising at altitude unrelated to hypoxia, such as frostbite and
    photokeratitis. Many of these conditions are discussed separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?15/42/16042?
    source=see_link\">",
    " \"High altitude, air travel, and heart disease\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?15/2/15396?
    source=see_link\">",
    " \"Photokeratitis\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?36/50/37671?
    source=see_link\">",
    " \"Frostbite\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?15/34/15913?
    source=see_link\">",
    " \"Accidental hypothermia in adults\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H15\">",
    " <span class=\"h1\">",
    " RISK FACTORS",
    " </span>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H16\">",
    " <span class=\"h2\">",
    " Individual",
    " </span>",
    " &nbsp;&mdash;&nbsp;Individual susceptibility to high altitude illness (HAI)
    varies widely for reasons that remain largely unexplained. Given adequate time,
    some individuals can acclimatize sufficiently to tolerate severe hypoxia, such as
    that found at the summit of Mt. Everest (8848 m or 29,029 ft; approximate PaO2 20
    to 30 mmHg). Others consistently develop debilitating AMS or HAPE during rapid
    ascent to elevations as low at 2500 m (approximate PaO2 60 to 70 mmHg).",
    " </p>",
    " <p>",
    " No reliable and easily available genetic or physiologic markers are able to
    predict an individual's susceptibility to HAI. Individual factors associated with
    an increased risk for HAI include (",
    " <a class=\"graphic graphic_table graphicRef65647 \" href=\"UTD.htm?
    8/55/9084\">",
    " table 4",
    " </a>",
    " ) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/1,17\">",
    " 1,17",
    " </a>",
    " ]:",
    " </p>",
    " <p>",
    " <ul class=\"bulletCompact-block\">",
    " <li>",
    " Past history of HAI (strongly predictive if conditions are similar)",
    " </li>",
    " <li>",
    " Rate of ascent",
    " </li>",
    " <li>",
    " Vigorous exertion prior to acclimatization",
    " </li>",
    " <li>",
    " Substances (eg, alcohol) or conditions that interfere with acclimatization",
    " </li>",
    " <li>",
    " Comorbidities that interfere with respiration (eg, neuromuscular disease) or
    circulation (eg, pulmonary hypertension)",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " HAI can be induced in any subject if the altitude is sufficiently high or the
    rate of ascent is sufficiently rapid, regardless of the person's capacity to
    acclimatize. Thus, the most important variables determining whether HAI develops
    are an individual's genetic susceptibility and the degree of hypoxic stress. The
    elevation attained (particularly the sleeping elevation) and the rate of ascent is
    of greatest importance when considering hypoxic stress. Conditions that further
    contribute to hypoxic stress, such as vigorous exertion prior to acclimatization,
    also increase the risk of HAI.",
    " </p>",
    " <p>",
    " Substances or conditions that interfere with sleep or respiratory function
    impair a person's ability to acclimatize to high altitude. Examples include
    sedative-hypnotic medications, alcohol, and sleep apnea. Comorbid conditions that
    impair ventilation, respiration, or oxygen-carrying capacity increase the risk for
    HAI. Examples include neuromuscular disease, COPD, restrictive lung disease, cystic
    fibrosis, pneumonia, pulmonary hypertension, and congenital cardiac anomalies
    involving right-to-left shunts [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/18-28\">",
    " 18-28",
    " </a>",
    " ]. Of note, neither anemia nor asthma is associated with an increased risk for
    HAI (in fact, asthma generally improves at high altitude). Sickle cell disease is
    exacerbated by hypoxic environments. Sickle cell disease and its complications are
    discussed separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?41/11/42170?
    source=see_link\">",
    " \"Overview of the clinical manifestations of sickle cell disease\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " HAI afflicts all ages and both genders, regardless of physical fitness.
    Younger athletes, particularly males, may be at greater risk of HAI for behavioral
    reasons. They are likely to engage in strenuous exertion prior to acclimatization
    or to pursue continued ascent, despite the presence of symptoms suggestive of HAI.
    Such behaviors feature prominently in severe and fatal cases of HAI.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H17\">",
    " <span class=\"h2\">",
    " Pediatric",
    " </span>",
    " &nbsp;&mdash;&nbsp;Some risk factors for high altitude illness apply to both
    young children and adults, but others play a greater role in the pediatric
    population and make them more susceptible to HAI. In infants under one year of age,
    HAI can lead to lethal complications.",
    " </p>",
    " <p>",
    " Shared risk factors among children and adults include the rate of ascent,
    absolute altitude achieved, degree of physical exertion, and colder ambient
    temperatures. Risk factors greater importance for the pediatric population relate
    to the unique physiology of hypoxia in infants and young children, as well as the
    effects of concurrent acquired or congenital conditions that are more prevalent in
    this age group (eg, upper respiratory infection, congenital cardiopulmonary
    disease, cystic fibrosis, Down syndrome). These issues are discussed in greater
    detail separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?27/7/27769?
    source=see_link&amp;anchor=H2#H2\">",
    " \"High altitude disease: Unique pediatric considerations\", section on 'High
    altitude physiology'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H10706307\">",
    " <span class=\"h2\">",
    " Pregnancy",
    " </span>",
    " &nbsp;&mdash;&nbsp;A relationship between pregnancy and high altitude illness
    has not been clearly established. Travel to moderate altitudes (up to 2500 m)
    during normal pregnancies appears safe. This issue is discussed in greater detail
    separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?41/1/42010?
    source=see_link&amp;anchor=H29#H29\">",
    " \"Initial prenatal assessment and patient education\", section on 'Travel to
    moderate and high altitudes'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Women residing at high altitudes have a greater risk of pregnancy-induced
    hypertension, proteinuria, and preeclampsia, and their newborns have lower birth
    weights [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/1\">",
    " 1",
    " </a>",
    " ]. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?10/23/10616?
    source=see_link&amp;anchor=H13#H13\">",
    " \"Overview of causes of and risk factors for fetal growth restriction\",
    section on 'Hypoxemia'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H18\">",
    " <span class=\"h2\">",
    " Environmental",
    " </span>",
    " &nbsp;&mdash;&nbsp;High altitude is commonly categorized according to the
    physiologic stress it produces (",
    " <a class=\"graphic graphic_table graphicRef63999 \" href=\"UTD.htm?
    8/24/8588\">",
    " table 1",
    " </a>",
    " and",
    " <a class=\"graphic graphic_table graphicRef50199 \" href=\"UTD.htm?0/4/71\">",
    " table 2",
    " </a>",
    " ). Although there is no consensus about such classification, the main concept
    is that progressive ascent results in increased hypoxic stress, requiring greater
    degrees of physiologic and behavioral adaptations in order to preserve function.",
    " </p>",
    " <p>",
    " In terms of HAI, symptoms generally do not manifest below 1500 m (5000 ft).
    From about 1500 to 2500 m (5000 to 8200 ft), symptoms are generally mild, if
    experienced at all. At 2500 m, symptoms of mild to moderate AMS become quite common
    among unacclimatized visitors after rapid ascent. At this altitude HAPE may also
    occur, but it is more common above 3000 m (9800 ft). Above 3000 to 4000 m (9800 to
    13,100 ft), AMS is common among people who have not properly acclimatized, and the
    risk of severe HAI, including life-threatening HAPE and HACE, is substantial.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H19\">",
    " <span class=\"h1\">",
    " PREVENTION",
    " </span>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H20\">",
    " <span class=\"h2\">",
    " General approach",
    " </span>",
    " &nbsp;&mdash;&nbsp;Most individuals ascend to high altitude with minimal or no
    symptoms by allowing sufficient time to acclimatize. A subset of patients benefits
    from pharmacologic prophylaxis. This includes those with a known predilection for
    HAI despite gradual ascent, and those who must ascend rapidly for convenience (eg,
    tourists traveling to mountain resort) or work (eg, rescue and military personnel).
    Pharmacologic prophylaxis is discussed separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?1/6/1130?
    source=see_link&amp;anchor=H28#H28\">",
    " \"Acute mountain sickness and high altitude cerebral edema\", section on
    'Pharmacologic prevention of AMS/HACE'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " When determining the optimal preventive strategy, factors to consider include
    the following [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/29\">",
    " 29",
    " </a>",
    " ]:",
    " </p>",
    " <p>",
    " <ul class=\"bulletCompact-block\">",
    " <li>",
    " Patient susceptibility (history of previous HAI)",
    " </li>",
    " <li>",
    " Medical history",
    " </li>",
    " <li>",
    " Medications and allergies",
    " </li>",
    " <li>",
    " Elevation of the person's usual residence",
    " </li>",
    " <li>",
    " Intended ascent profile (ie, rapid or gradual ascent)",
    " </li>",
    " <li>",
    " Purpose of ascent",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H21\">",
    " <span class=\"h2\">",
    " Behavioral methods",
    " </span>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H22\">",
    " <span class=\"h3\">",
    " Gradual ascent",
    " </span>",
    " &nbsp;&mdash;&nbsp;Gradual ascent is the surest and safest method of
    preventing or ameliorating HAI [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/30,31\">",
    " 30,31",
    " </a>",
    " ]. As a general guideline, individuals who normally reside below 1500 m (5000
    ft) elevation should avoid an abrupt ascent to sleeping altitudes above 2800 m
    (9200 ft). This is best accomplished by spending one night at an intermediate
    altitude (particularly when traveling to an elevation that caused symptoms
    previously).",
    " </p>",
    " <p>",
    " If further ascent above 3000 m (9800 ft) is planned, we suggest not spending
    subsequent nights at elevations over 500 m higher than the previous night, and
    including a rest day (no ascent and no vigorous activity) for every 1000 m (3280
    ft) climbed. Even this conservative approach may prove too aggressive for
    individuals particularly susceptible to HAI [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/32\">",
    " 32",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " A common adage among mountaineers is \"climb high, sleep low.\" Day trips to
    higher elevation with a return to a lower altitude for sleep may accelerate
    acclimatization.",
    " </p>",
    " <p>",
    " Another strategy is preexposure. Residing at a site above 1500 m or
    participating in brief climbs to elevations over 1500 m (4920 ft) in the weeks
    leading up to a trip to higher elevations provides a degree of preacclimatization,
    and may allow for a faster rate of ascent [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/1,33,34\">",
    " 1,33,34",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H23\">",
    " <span class=\"h3\">",
    " Education",
    " </span>",
    " &nbsp;&mdash;&nbsp;Individuals with a history of HAI or significant
    cardiopulmonary disease should be counseled regarding their increased risk and be
    provided with a conservative ascent plan (or profile). The clinician and patient
    should review this profile and discuss the relative risks associated with each
    elevation, as well as the risks of limited accessibility to medical care and
    evacuation.",
    " </p>",
    " <p>",
    " Educating patients about the early symptoms and signs of HAI and the need for
    prompt intervention, particularly with regard to HAPE and HACE, can be life-saving
    [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/5,6,35\">",
    " 5,6,35",
    " </a>",
    " ]. Patients should commit to memory the mantra that no one with symptoms of
    HAI should continue to ascend, and that descent is mandatory if symptoms do not
    improve. A plan of action in the event that immediate descent is not possible
    should be discussed.",
    " </p>",
    " <p>",
    " Health care workers who advise travelers need to understand the best
    prevention strategies and treatment options based upon variables, such as ascent
    profile (rate of ascent, ultimate elevation attained, time spent at various
    elevations), previous history of HAI, comorbidities, medication allergies, severity
    of illness (AMS versus HAPE or HACE), treatment setting (eg, terrain, weather,
    remoteness), and available treatment options (eg, field, clinic, hospital) (",
    " <a class=\"graphic graphic_table graphicRef50199 \" href=\"UTD.htm?0/4/71\">",
    " table 2",
    " </a>",
    " ). Individuals should be informed that the process of acclimatization is
    hindered by the use of respiratory depressants (eg, sedatives) or alcohol and by
    overexertion during the first few days at high altitude.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H24\">",
    " <span class=\"h3\">",
    " Alcohol and drug use",
    " </span>",
    " &nbsp;&mdash;&nbsp;Alcohol and sedative-hypnotics should be avoided during the
    acclimatization process, particularly during the first two nights at a new
    elevation. Both types of agents depress respiratory function and interfere with
    normal sleep patterns and physiologic responses to altitude, which are necessary
    for acclimatization.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H25\">",
    " <span class=\"h3\">",
    " Diet and hydration",
    " </span>",
    " &nbsp;&mdash;&nbsp;Various diets, including high carbohydrate, have been
    touted to reduce the incidence of HAI, but data are inconclusive [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/1\">",
    " 1",
    " </a>",
    " ]. Similarly, vigorous hydration, beyond the amount required to maintain
    adequate hydration, has not been shown to reduce the incidence of HAI [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/6,36,37\">",
    " 6,36,37",
    " </a>",
    " ]. Climbers should be aware of the risk of hyponatremia when
    following \"conventional wisdom\" about vigorous hydration. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?3/30/3562?
    source=see_link\">",
    " \"Causes of hyponatremia\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H26\">",
    " <span class=\"h3\">",
    " Exertion",
    " </span>",
    " &nbsp;&mdash;&nbsp;Vigorous exertion at altitude contributes to the
    development of AMS as well as HAPE, although sedentary persons also develop these
    illnesses [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/38\">",
    " 38",
    " </a>",
    " ]. Modest exercise may aid acclimatization [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/297/abstract/1,6,38,39\">",
    " 1,6,38,39",
    " </a>",
    " ]. Patients with a previous history of HAI should be particularly wary of
    vigorous exertion during the first few days at high altitude.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H27\">",
    " <span class=\"h2\">",
    " Pharmacologic prophylaxis",
    " </span>",
    " &nbsp;&mdash;&nbsp;Clinicians should reserve prophylactic medications for
    individuals with a history of altitude intolerance and those who must make a
    planned rapid ascent to high altitude. Even in individuals with a previous history
    of HAI, gradual ascent should be emphasized over pharmacologic prophylaxis. Often,
    ascending at a slower rate than the previous offending ascent allows individuals to
    avoid illness.",
    " </p>",
    " <p>",
    " Patients with comorbid conditions that are exacerbated by hypoxic environments
    (eg, ischemic heart disease, COPD, sickle cell disease, cystic fibrosis) who wish
    to travel to moderate altitudes may warrant prophylactic oxygen therapy. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?15/42/16042?
    source=see_link\">",
    " \"High altitude, air travel, and heart disease\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?28/10/28840?
    source=see_link\">",
    " \"Traveling with oxygen aboard commercial air carriers\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?38/26/39338?
    source=see_link\">",
    " \"Management of stable chronic obstructive pulmonary disease\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?41/11/42170?
    source=see_link\">",
    " \"Overview of the clinical manifestations of sickle cell disease\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Pharmacologic prophylaxis against HAI is discussed separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?1/6/1130?
    source=see_link&amp;anchor=H28#H28\">",
    " \"Acute mountain sickness and high altitude cerebral edema\", section on
    'Pharmacologic prevention of AMS/HACE'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"PATIENT_INFORMATION\">",
    " <span class=\"h1\">",
    " INFORMATION FOR PATIENTS",
    " </span>",
    " &nbsp;&mdash;&nbsp;UpToDate offers two types of patient education materials,
    &ldquo;The Basics&rdquo; and &ldquo;Beyond the Basics.&rdquo; The Basics patient
    education pieces are written in plain language, at the 5",
    " <sup>",
    " th",
    " </sup>",
    " to 6",
    " <sup>",
    " th",
    " </sup>",
    " grade reading level, and they answer the four or five key questions a patient
    might have about a given condition. These articles are best for patients who want a
    general overview and who prefer short, easy-to-read materials. Beyond the Basics
    patient education pieces are longer, more sophisticated, and more detailed. These
    articles are written at the 10",
    " <sup>",
    " th",
    " </sup>",
    " to 12",
    " <sup>",
    " th",
    " </sup>",
    " grade reading level and are best for patients who want in-depth information
    and are comfortable with some medical jargon.",
    " </p>",
    " <p>",
    " Here are the patient education articles that are relevant to this topic. We
    encourage you to print or e-mail these topics to your patients. (You can also
    locate patient education articles on a variety of subjects by searching on
    &ldquo;patient info&rdquo; and the keyword(s) of interest.)",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Basics topic (see",
    " <a class=\"medical medical_basics\" href=\"UTD.htm?23/18/23842?
    source=see_link\">",
    " \"Patient information: Altitude sickness (including mountain sickness) (The
    Basics)\"",
    " </a>",
    " )",
    " </li>",
    " <li>",
    " Beyond the Basics topic (see",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?4/19/4403?
    source=see_link\">",
    " \"Patient information: High altitude illness (including mountain sickness)
    (Beyond the Basics)\"",
    " </a>",
    " )",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H29\">",
    " <span class=\"h1\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </span>",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " The arterial partial pressure of oxygen (PaO2) decreases with altitude,
    resulting in progressive tissue hypoxia. The normal compensatory response to
    hypobaric hypoxia is termed acclimatization. The capacity to acclimatize varies
    greatly among individuals and is dependent upon many factors, including the degree
    of hypoxic stress (rate of ascent, altitude attained), the intrinsic capacity of
    the individual to compensate for diminished PaO2, and extrinsic factors. The
    process begins within minutes of ascent but requires several weeks to complete.
    (See",
    " <a class=\"local\" href=\"#H2\">",
    " 'High altitude physiology'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " High altitude illness (HAI) is the collective term for the pathologic
    syndromes that can develop following an initial ascent to high altitude or
    following a further ascent while already at high altitude. HAI includes acute
    mountain sickness (AMS) and high altitude cerebral edema (HACE), which afflict the
    brain, and high altitude pulmonary edema (HAPE), which afflicts the lungs. (See",
    " <a class=\"local\" href=\"#H10\">",
    " 'Definitions'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Individual factors associated with an increased risk for HAI include:",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " <ul class=\"hyphen-block\">",
    " <li>",
    " Past history of HAI (strongly predictive if conditions are similar)",
    " </li>",
    " <li>",
    " Rate of ascent",
    " </li>",
    " <li>",
    " Vigorous exertion prior to acclimatization",
    " </li>",
    " <li>",
    " Substances (eg, alcohol) or conditions that interfere with acclimatization",
    " </li>",
    " <li>",
    " Comorbidities that interfere with respiration (eg, neuromuscular disease) or
    circulation (eg, pulmonary hypertension) (see",
    " <a class=\"local\" href=\"#H16\">",
    " 'Individual'",
    " </a>",
    " above)",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Progressive ascent results in increased hypoxic stress, requiring greater
    degrees of physiologic and behavioral adaptations in order to preserve function.
    The more rapid the ascent and the higher the altitude, the greater the stress.
    (See",
    " <a class=\"local\" href=\"#H18\">",
    " 'Environmental'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Most individuals ascend to high altitude without complications by allowing
    sufficient time to acclimatize. Patients with a known predilection for HAI despite
    gradual ascent, and others who must ascend rapidly for convenience (eg, tourists
    traveling to mountain resort) or work (eg, rescue personnel) may benefit from
    pharmacologic prophylaxis, which is discussed separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?28/16/28936?
    source=see_link&amp;anchor=H24#H24\">",
    " \"High altitude pulmonary edema\", section on 'Prophylactic medications'",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?1/6/1130?
    source=see_link&amp;anchor=H28#H28\">",
    " \"Acute mountain sickness and high altitude cerebral edema\", section on
    'Pharmacologic prevention of AMS/HACE'",
    " </a>",
    " .)",
    " </li>",
    " <li>",
    " Gradual ascent is the surest and safest method of preventing or ameliorating
    HAI. As a general guideline, individuals who normally reside below 1500 m (5000 ft)
    elevation should avoid an abrupt ascent to sleeping altitudes above 2800 m (9200
    ft). Alcohol and sedative-hypnotics should be avoided during acclimatization.
    Vigorous exertion at altitude contributes to the development of both AMS and HAPE,
    and should also be avoided during acclimatization. Additional preventive strategies
    are discussed in the text. (See",
    " <a class=\"local\" href=\"#H19\">",
    " 'Prevention'",
    " </a>",
    " above.)",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H94660212\">",
    " <span class=\"h1\">",
    " ACKNOWLEDGMENT",
    " </span>",
    " &nbsp;&mdash;&nbsp;We are saddened by the untimely death of John Marx, MD, who
    passed away in July 2012. We wish to acknowledge Dr. Marx's dedication and his many
    contributions to UpToDate, in particular, his work as editor-in-chief for Emergency
    Medicine and as a section editor and author for Adult Trauma.",
    " </p>",
    " </div>",
    " <div id=\"topicAgreement\">",
    " Use of UpToDate is subject to the",
    " <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
    target=\"_blank\">",
    " Subscription and License Agreement",
    " </a>",
    " .",
    " </div>",
    " <div class=\"headingAnchor\" id=\"references\">",
    " <h1>",
    " REFERENCES",
    " </h1>",
    " <ol id=\"reference\">",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/297/abstract/2\">",
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    " Johnson PL, Popa DA, Prisk GK, et al. Non-invasive positive pressure
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    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/297/abstract/12\">",
    " Bloch KE, Latshang TD, Turk AJ, et al. Nocturnal periodic breathing during
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    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/297/abstract/13\">",
    " K&uuml;pper T, Sch&ouml;ffl V, Netzer N. Cheyne stokes breathing at high
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    mountain sickness. Am J Med 1979; 67:214.",
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    " Butler FK, Harris DJ Jr, Reynolds RD. Altitude retinopathy on Mount Everest,
    1989. Ophthalmology 1992; 99:739.",
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    " Lang GE, Kuba GB. High-altitude retinopathy. Am J Ophthalmol 1997;
    123:418.",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/297/abstract/17\">",
    " Hackett PH, Roach RC. High-altitude illness. N Engl J Med 2001; 345:107.",
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    " Duster MC, Derlet MN. High-altitude illness in children. Pediatr Ann 2009;
    38:218.",
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    " Durmowicz AG, Noordeweir E, Nicholas R, Reeves JT. Inflammatory processes
    may predispose children to high-altitude pulmonary edema. J Pediatr 1997;
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    " Choudhuri JA, Ogden LG, Ruttenber AJ, et al. Effect of altitude on
    hospitalizations for respiratory syncytial virus infection. Pediatrics 2006;
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    " Fasules JW, Wiggins JW, Wolfe RR. Increased lung vasoreactivity in children
    from Leadville, Colorado, after recovery from high-altitude pulmonary edema.
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    " Lovering AT, Romer LM, Haverkamp HC, et al. Excessive gas exchange
    impairment during exercise in a subject with a history of bronchopulmonary
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/297/abstract/23\">",
    " Rios B, Driscoll DJ, McNamara DG. High-altitude pulmonary edema with absent
    right pulmonary artery. Pediatrics 1985; 75:314.",
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    " Sebbane M, Wuyam B, Pin I, et al. Unilateral agenesis of the pulmonary
    artery and high-altitude pulmonary edema (HAPE) at moderate altitude. Pediatr
    Pulmonol 1997; 24:111.",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/297/abstract/25\">",
    " Oades PJ, Buchdahl RM, Bush A. Prediction of hypoxaemia at high altitude in
    children with cystic fibrosis. BMJ 1994; 308:15.",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/297/abstract/26\">",
    " Pashankar FD, Carbonella J, Bazzy-Asaad A, Friedman A. Prevalence and risk
    factors of elevated pulmonary artery pressures in children with sickle cell
    disease. Pediatrics 2008; 121:777.",
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    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/297/abstract/27\">",
    " Hultgren HN, Honigman B, Theis K, Nicholas D. High-altitude pulmonary edema
    at a ski resort. West J Med 1996; 164:222.",
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    " Das BB, Wolfe RR, Chan KC, et al. High-altitude pulmonary edema in children
    with underlying cardiopulmonary disorders and pulmonary hypertension living at
    altitude. Arch Pediatr Adolesc Med 2004; 158:1170.",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/297/abstract/29\">",
    " Luks AM, McIntosh SE, Grissom CK, et al. Wilderness Medical Society
    consensus guidelines for the prevention and treatment of acute altitude illness.
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/297/abstract/30\">",
    " Bloch KE, Turk AJ, Maggiorini M, et al. Effect of ascent protocol on acute
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    " Beidleman BA, Fulco CS, Muza SR, et al. Effect of six days of staging on
    physiologic adjustments and acute mountain sickness during ascent to 4300 meters.
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    " Pesce C, Leal C, Pinto H, et al. Determinants of acute mountain sickness and
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    " Schneider M, Bernasch D, Weymann J, et al. Acute mountain sickness:
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    " Honigman B, Theis MK, Koziol-McLain J, et al. Acute mountain sickness in a
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    " Graham LE, Basnyat B. Cerebral edema in the Himalayas: too high, too fast!
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    " Basnyat B, Lemaster J, Litch JA. Everest or bust: a cross sectional,
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    " Swenson ER, MacDonald A, Vatheuer M, et al. Acute mountain sickness is not
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/297/abstract/38\">",
    " Roach RC, Maes D, Sandoval D, et al. Exercise exacerbates acute mountain
    sickness at simulated high altitude. J Appl Physiol 2000; 88:581.",
    " </a>",
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    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/297/abstract/39\">",
    " MENON ND. HIGH-ALTITUDE PULMONARY EDEMA: A CLINICAL STUDY. N Engl J Med
    1965; 273:66.",
    " </a>",
    " </li>",
    " </ol>",
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    var outline_f0_18_297=[" <div id=\"toggleOutline\">",
    " <a href=\"#\" title=\"Collapse Topic Outline\">",
    " <img alt=\"\" src=\"./../images/orange_arrow_left.myextg\"/>",
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    " <h1>",
    " TOPIC OUTLINE",
    " </h1>",
    " <div id=\"outline\">",
    " <ul>",
    " <li>",
    " <a class=\"sr_button\" href=\"#H29\" id=\"summRecButton\">",
    " <span>",
    " SUMMARY &amp; RECOMMENDATIONS",
    " </span>",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H1\">",
    " INTRODUCTION",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H2\">",
    " HIGH ALTITUDE PHYSIOLOGY",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H3\">",
    " Hypobaric hypoxia",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H4\">",
    " Acclimatization",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H5\">",
    " - Overview",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H6\">",
    " - Ventilation and PaO2",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H7\">",
    " - Circulatory changes",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H8\">",
    " - Hematologic changes",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H9\">",
    " - Oxygen delivery and utilization",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H10\">",
    " DEFINITIONS",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H11\">",
    " High altitude illness",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H12\">",
    " Acute mountain sickness and high altitude cerebral edema",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H13\">",
    " High altitude pulmonary edema",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H14\">",
    " Other altitude-related illnesses",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H15\">",
    " RISK FACTORS",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H16\">",
    " Individual",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H17\">",
    " Pediatric",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H10706307\">",
    " Pregnancy",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H18\">",
    " Environmental",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H19\">",
    " PREVENTION",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H20\">",
    " General approach",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H21\">",
    " Behavioral methods",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H22\">",
    " - Gradual ascent",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H23\">",
    " - Education",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H24\">",
    " - Alcohol and drug use",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H25\">",
    " - Diet and hydration",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H26\">",
    " - Exertion",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H27\">",
    " Pharmacologic prophylaxis",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#PATIENT_INFORMATION\">",
    " INFORMATION FOR PATIENTS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H29\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H94660212\">",
    " ACKNOWLEDGMENT",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " <div class=\"openRelatedGraphics\" id=\"EM/181\" rel=\"outline_link\">",
    " GRAPHICS",
    " <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
    " View All",
    " </a>",
    " </div>",
    " </h1>",
    " <div id=\"relatedGraphics\">",
    " <ul>",
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    " <a href=\"#\" title=\"FIGURES\">",
    " FIGURES",
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    " </div>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_figure\" href=\"UTD.htm?29/55/30590\"
    title=\"figure 1\">",
    " Oxygenation at different altitudes",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <div class=\"openRelatedGraphics\" id=\"EM/181|TAB\">",
    " <a href=\"#\" title=\"TABLES\">",
    " TABLES",
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    " <a class=\"graphic graphic_table\" href=\"UTD.htm?8/24/8588\" title=\"table
    1\">",
    " Physiologic effects of high altitude",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?0/4/71\" title=\"table
    2\">",
    " High altitude sites",
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    " <a class=\"graphic graphic_table\" href=\"UTD.htm?40/28/41420\" title=\"table
    3\">",
    " Diseases caused or exacerbated by high altitude",
    " </a>",
    " </li>",
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    " <a class=\"graphic graphic_table\" href=\"UTD.htm?8/55/9084\" title=\"table
    4\">",
    " Risk for high altitude illness",
    " </a>",
    " </li>",
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    " </div>",
    " <h1>",
    " RELATED TOPICS",
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    var title_f0_18_298="Clinical manifestations and diagnosis of Behçet’s disease";
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    " Yusuf Yazici, MD",
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    href=\"UTD.htm?0/18/298/contributors\">",
    " Section Editor",
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    0/18/298/contributors\">",
    " John H Stone, MD, MPH",
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    href=\"UTD.htm?0/18/298/contributors\">",
    " Deputy Editor",
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    0/18/298/contributors\">",
    " Paul L Romain, MD",
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    " Disclosures",
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    " <span>",
    " All topics are updated as new evidence becomes available and our",
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    " peer review process",
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    " <span class=\"emphasis\">",
    " Literature review current through:",
    " </span>",
    " Oct 2013.",
    " <span class=\"pipeSpace\">",
    " |",
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    " This topic last updated:",
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    " Sep 24, 2012.",
    " </div>",
    " <div id=\"topicText\">",
    " <p class=\"headingAnchor\" id=\"H1\">",
    " <span class=\"h1\">",
    " INTRODUCTION",
    " </span>",
    " &nbsp;&mdash;&nbsp;Beh&ccedil;et&rsquo;s disease is characterized by recurrent
    oral aphthae and any of several systemic manifestations including genital aphthae,
    ocular disease, skin lesions, gastrointestinal involvement, neurologic disease,
    vascular disease, or arthritis. Beh&ccedil;et&rsquo;s may have been described by
    Hippocrates but was brought to the attention of the modern medical community by
    Hulusi Beh&ccedil;et in 1937 [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/1-3\">",
    " 1-3",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Most clinical manifestations of Beh&ccedil;et&rsquo;s disease are believed to
    be due to vasculitis. Among the systemic vasculitides, Beh&ccedil;et&rsquo;s
    disease is remarkable for its ability to involve blood vessels of all sizes (small,
    medium, and large) on both the arterial and venous sides of the circulation.",
    " </p>",
    " <p>",
    " The clinical manifestations, diagnosis, and differential diagnosis of
    Beh&ccedil;et&rsquo;s disease are reviewed here. The pathogenesis and treatment of
    this disorder are discussed separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?28/12/28874?
    source=see_link\">",
    " \"Pathogenesis of Beh&ccedil;et&rsquo;s disease\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?32/45/33498?
    source=see_link\">",
    " \"Treatment of Beh&ccedil;et&rsquo;s disease\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H591878\">",
    " <span class=\"h1\">",
    " EPIDEMIOLOGY",
    " </span>",
    " &nbsp;&mdash;&nbsp;Beh&ccedil;et&rsquo;s disease is more common (and often
    more severe) along the ancient silk road, which extends from eastern Asia to the
    Mediterranean [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/4,5\">",
    " 4,5",
    " </a>",
    " ]. It is most common in Turkey (80 to 370 cases per 100,000) while the
    prevalence ranges from 13.5 to 35 per 100,000 in Japan, Korea, China, Iran, Iraq,
    and Saudi Arabia [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/4\">",
    " 4",
    " </a>",
    " ]. By comparison, the prevalence is from 1 per 15,000 to 1 per 500,000 in
    North American (Olmsted County, Minnesota) and Northern European countries [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/6\">",
    " 6",
    " </a>",
    " ]. The prevalence is similar in men and women in the areas where it is more
    common, but women are affected more commonly in reports from the United States and
    northern Europe. It typically affects young adults 20 to 40 years of age but is
    infrequently also seen in children [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/7-9\">",
    " 7-9",
    " </a>",
    " ]. The disease appears to be more severe in young, male, and Middle Eastern or
    Far Eastern patients [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/10-16\">",
    " 10-16",
    " </a>",
    " ]. Most cases of Beh&ccedil;et&rsquo;s are sporadic, although families with
    multiple affected members, which is known as familial clustering, have been
    reported, and having a first degree relative with Beh&ccedil;et&rsquo;s does
    increase risk for the disease [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/17,18\">",
    " 17,18",
    " </a>",
    " ]. Earlier onset of disease in successive generations, known as genetic
    anticipation, has been described [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/19\">",
    " 19",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H2\">",
    " <span class=\"h1\">",
    " CLINICAL MANIFESTATIONS",
    " </span>",
    " &nbsp;&mdash;&nbsp;The common clinical feature in patients with
    Beh&ccedil;et&rsquo;s disease is the presence of recurrent and usually painful
    mucocutaneous ulcers. Other clinical manifestations of this disorder are more
    variable among different patients and populations.",
    " </p>",
    " <p>",
    " Severity is generally greater in men. The greatest morbidity and mortality
    occur with ocular disease (affecting up to two-thirds of patients), vascular
    disease (affecting up to one-third of patients), and central nervous system disease
    (affecting 10 to 20 percent of patients). Cutaneous and articular manifestations
    are common. Renal disease and peripheral nervous system involvement are rare
    compared with other vasculitides [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/20\">",
    " 20",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Although there are limited data on children with Beh&ccedil;et's disease,
    clinical manifestations appear to generally be similar to those in adults [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/7-9\">",
    " 7-9",
    " </a>",
    " ]. Among some populations, there may be differences in the frequencies or
    types of certain manifestations, including neurologic disease [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/9,21\">",
    " 9,21",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H3\">",
    " <span class=\"h2\">",
    " Oral ulcerations",
    " </span>",
    " &nbsp;&mdash;&nbsp;Most, but not all, patients initially manifest recurrent
    oral aphthous ulcerations (also known as canker sores), which are grossly and
    histologically similar to common oral ulcers and recurrent aphthous stomatitis
    (RAS) but which tend to be more extensive and often multiple (",
    " <a class=\"graphic graphic_picture graphicRef76223 \" href=\"UTD.htm?
    9/62/10222\">",
    " picture 1",
    " </a>",
    " ). The ulcers are characteristically painful and, in severe cases, may limit
    eating. They are rounded and range in size from a few millimeters to 2 centimeters.
    They have well-defined borders, have a white-yellow necrotic base, and may have
    surrounding erythema. Minor ulcers are defined as those less than 1 cm in diameter,
    and major ulcers are defined as those at least 1 cm in diameter. Major ulcers may
    scar. Outer portions of the lips are not involved.",
    " </p>",
    " <p>",
    " Oral ulceration that recurs more than three times in one year is required to
    meet the diagnostic criteria for Beh&ccedil;et&rsquo;s disease. (See",
    " <a class=\"local\" href=\"#H16\">",
    " 'Diagnosis'",
    " </a>",
    " below.). Healing of oral ulcers is typically spontaneous within one to three
    weeks; with recurrent lesions, however, some patients will have ulcers present
    continuously. Oral ulcers are typically the first to come and last to leave in the
    course of the disease; they may become less common after about 20 years [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/12\">",
    " 12",
    " </a>",
    " ]. They may be a less frequent manifestation in cigarette smokers [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/22\">",
    " 22",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H4\">",
    " <span class=\"h2\">",
    " Urogenital lesions",
    " </span>",
    " &nbsp;&mdash;&nbsp;Genital ulceration occurs in 75 percent or more of patients
    with Beh&ccedil;et&rsquo;s disease. The ulcers are similar in appearance to the
    oral aphthae and are usually painful. Genital ulcers are most commonly found on the
    scrotum in men and the vulva in women, although any mucous membrane may be involved
    (",
    " <a class=\"graphic graphic_picture graphicRef81014 \" href=\"UTD.htm?
    31/47/32497\">",
    " picture 2",
    " </a>",
    " ). Recurrence is typically less frequent than with oral ulcerations. Scar
    formation is frequent for genital lesions. Scrotal scarring secondary to ulcers is
    rarely, if ever, seen in conditions other than Beh&ccedil;et&rsquo;s disease.",
    " </p>",
    " <p>",
    " Epididymitis, salpingitis, varicocele, and other genitourinary inflammatory
    conditions may also occur in patients with this disorder [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/23,24\">",
    " 23,24",
    " </a>",
    " ]. Urethritis is an unusual feature.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H5\">",
    " <span class=\"h2\">",
    " Cutaneous lesions",
    " </span>",
    " &nbsp;&mdash;&nbsp;Cutaneous lesions also occur in over 75 percent of patients
    with Beh&ccedil;et&rsquo;s disease. The skin manifestations vary and may include
    acneiform lesions, papulo-vesiculo-pustular eruptions, pseudofolliculitis, nodules,
    erythema nodosum (septal panniculitis), superficial thrombophlebitis, pyoderma
    gangrenosum-type lesions, erythema multiforme-like lesions, and palpable purpura.
    Biopsy of erythema nodosum lesions reveals a septal panniculitis, with medium
    vessel vasculitis in up to half of lesions [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/25\">",
    " 25",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Acneiform lesions may be more common in those with associated arthritis [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/26,27\">",
    " 26,27",
    " </a>",
    " ]. These lesions consist of papules and pustules that are indistinguishable
    from ordinary acne and share characteristic microbiologic flora with papulopustular
    lesions of acne [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/28\">",
    " 28",
    " </a>",
    " ]. Pustular skin lesions are often not sterile and may contain Staphylococcus
    aureus and Prevotella spp [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/28\">",
    " 28",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Pathergy refers to an erythematous papular or pustular response to local skin
    injury. It is defined as a pustule-like lesion or papule that appears 48 hours
    after skin prick by a 20 gauge needle. Pathergy is less common in North American
    and North European patients with Beh&ccedil;et&rsquo;s disease (10 to 20 percent)
    than in patients from more endemic areas (50 to 75 percent). Dermographism is a
    response to light scratching of the skin that may be present in some patients [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/29\">",
    " 29",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Nailfold capillary abnormalities occurred in 75 percent of 33 patients with
    Beh&ccedil;et&rsquo;s disease in one study compared with 7 percent of normal
    controls [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/30\">",
    " 30",
    " </a>",
    " ]. The degree of abnormality correlated with the degree of skin disease and
    arthritis.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H6\">",
    " <span class=\"h2\">",
    " Ocular disease",
    " </span>",
    " &nbsp;&mdash;&nbsp;Ocular disease occurs in 25 to 75 percent of patients with
    Beh&ccedil;et&rsquo;s disease, depending upon the population studied, and, in most
    cases, progresses to blindness if not treated. Ocular disease typically is less
    severe in North American populations, resulting in a lower incidence of vision loss
    [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/31\">",
    " 31",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Uveitis is often the dominant feature of Beh&ccedil;et&rsquo;s disease. It
    is typically bilateral and episodic, often involves the entire uveal tract (pan
    uveitis), and may not resolve completely between episodes. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?23/16/23817?
    source=see_link\">",
    " \"Uveitis: Etiology, clinical manifestations, and diagnosis\"",
    " </a>",
    " .)",
    " </li>",
    " <li>",
    " Hypopyon is a severe anterior uveitis with purulent material in the anterior
    chamber that is characteristically seen in about 20 percent of patients with
    Beh&ccedil;et&rsquo;s disease. Many patients with hypopyon will demonstrate retinal
    vasculitis [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/32\">",
    " 32",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Posterior uveitis, retinal vasculitis (",
    " <a class=\"graphic graphic_picture graphicRef64705 graphicRef63242 \"
    href=\"UTD.htm?1/14/1250\">",
    " picture 3A-B",
    " </a>",
    " ), vascular occlusion, and optic neuritis require systemic immunosuppressive
    treatment and may irreversibly impair vision and progress to blindness if
    untreated.",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Other changes that can be seen include neovascularization, secondary
    cataracts, glaucoma, frosted branch angiitis, and, in approximately 3 percent of
    patients, conjunctival ulceration [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/33,34\">",
    " 33,34",
    " </a>",
    " ]. Neovascularization most commonly occurs due to inflammation, and treatment
    with immunosuppression, particularly with interferon, may be beneficial [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/35\">",
    " 35",
    " </a>",
    " ]. Conjunctivitis, scleritis, episcleritis, and sicca syndrome are uncommon.",
    " </p>",
    " <p>",
    " In a retrospective review of 880 Turkish patients with Beh&ccedil;et&rsquo;s
    uveitis, 68 percent were male, and the mean age of onset was 28.5 years for men and
    30 for women. Ocular disease was bilateral in 78.1 percent, and panuveitis was the
    most common finding. Risk of losing useful vision at 10 years was 30 percent for
    men and 17 percent for women, but prognosis was better in the 1990s than in the
    1980s [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/36\">",
    " 36",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " A retrospective review of childhood onset uveitis in 36 Beh&ccedil;et&rsquo;s
    patients reported diagnostic and treatment findings similar to those seen in adults
    [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/8\">",
    " 8",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H7\">",
    " <span class=\"h2\">",
    " Neurologic disease",
    " </span>",
    " &nbsp;&mdash;&nbsp;Neurologic disease occurs in less than one-fifth of
    patients with Beh&ccedil;et&rsquo;s disease [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/37-40\">",
    " 37-40",
    " </a>",
    " ]. It is observed more frequently in men than women. Focal parenchymal lesions
    and complications of vascular thrombosis are the most common abnormalities. Other
    manifestations include epileptic seizures, aseptic meningitis, encephalitis, and
    arterial vasculitis. Progressive personality change, psychiatric disorders, and
    dementia may develop. Unlike many other systemic vasculitic disorders, peripheral
    neuropathy is not a common feature of Beh&ccedil;et&rsquo;s disease, though it may
    develop in a subset of patients [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/41-43\">",
    " 41-43",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Focal neurologic manifestations may be due to lesions in the corticospinal
    tract, brainstem, periventricular white matter, spinal cord, and basal ganglia.
    Cerebellar involvement, though reported, is unusual. These central nervous system
    lesions are detectable with magnetic resonance imaging (MRI) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/37,44\">",
    " 37,44",
    " </a>",
    " ]. Pathology reveals local perivenular lymphocytic cuffing, inflammatory cell
    infiltration, gliosis, necrosis, and neuronal loss. Although frank vasculitis is
    not always observed in parenchymal lesions, it is sometimes noted in larger
    cerebral vessels, including arteries or veins. Arteritis may lead to ischemic
    strokes, dissection, aneurysmal dilatation, and subarachnoid hemorrhage.",
    " </p>",
    " <p>",
    " Central nervous system manifestations may result from arterial or venous
    thrombosis, including dural sinus thrombosis [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/45\">",
    " 45",
    " </a>",
    " ]. Cerebral venous thrombosis may present with headache, papilledema, sixth
    nerve palsy, and an elevated cerebrospinal fluid (CSF) pressure [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/12,13,37,45-47\">",
    " 12,13,37,45-47",
    " </a>",
    " ]. An association has been observed between dural sinus thrombosis and
    peripheral deep venous thrombosis [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/37\">",
    " 37",
    " </a>",
    " ]. Thrombosis of the cerebral arteries may also be observed [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/37,45\">",
    " 37,45",
    " </a>",
    " ]. One analysis of neurologic Beh&ccedil;et&rsquo;s from Turkey, involving 26
    children and 702 adults, found that dural venous sinus thrombosis was much more
    common in children than parenchymal neurologic involvement, although parenchymal
    disease was more frequent in adults [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/21\">",
    " 21",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " In one large series, the clinical features and outcomes of 200 patients with
    Beh&ccedil;et&rsquo;s disease and neurologic involvement were reported [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/37\">",
    " 37",
    " </a>",
    " ]. On average, a period of approximately five to six years elapsed between the
    onset of the earliest non-neurologic symptoms of Beh&ccedil;et&rsquo;s disease and
    the appearance of neurologic symptoms or findings. Nevertheless, neurologic
    findings may also appear concurrently (7.5 percent) or precede non-neurologic
    features (3 percent). Twenty percent of those with neurologic findings were
    asymptomatic.",
    " </p>",
    " <p>",
    " The prognosis varies with the type of neurologic process. Those with dural
    venous thrombosis or other non-parenchymal processes are less likely to have
    recurrent disease, disability, or premature death. By comparison, patients with
    parenchymal disease have a worse outcome [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/37,48\">",
    " 37,48",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Cerebrospinal fluid (CSF) analysis may also help determine prognosis. In one
    study, roughly 90 percent of those with elevated CSF protein levels or CSF
    pleocytosis had additional neurologic events, progressive disability, or death
    during at least three years of follow-up. Only 25 to 30 percent of those with
    normal CSF protein levels suffered one such event [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/37\">",
    " 37",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H8\">",
    " <span class=\"h2\">",
    " Vascular disease",
    " </span>",
    " &nbsp;&mdash;&nbsp;Most clinical manifestations of Beh&ccedil;et&rsquo;s
    disease are believed to be due to vasculitis, and Beh&ccedil;et&rsquo;s disease is
    remarkable for its ability to involve blood vessels of all sizes (small, medium,
    and large) on both the arterial and venous sides of the circulation. Vascular
    disease in Beh&ccedil;et&rsquo;s is more common in men.",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Arterial disease is most commonly a small vessel vasculitis, but medium and
    large vessel disease may also develop.",
    " <br/>",
    " <br/>",
    " Large vessel vascular involvement occurs in approximately one-third of
    patients with Beh&ccedil;et&rsquo;s disease [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/49\">",
    " 49",
    " </a>",
    " ]. In these patients, perivascular and endovascular inflammation may lead to
    hemorrhage, stenosis, aneurysm formation, thrombus formation in both arteries and
    veins, and varices. Progression and recurrence are more likely in these patients,
    and immunosuppressive treatment of this inflammation has been found to be
    beneficial, though patients may also require vascular surgery intervention (",
    " <a class=\"graphic graphic_table graphicRef68660 \" href=\"UTD.htm?
    9/6/9324\">",
    " table 1",
    " </a>",
    " ) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/50\">",
    " 50",
    " </a>",
    " ].",
    " <br/>",
    " <br/>",
    " Carotid, pulmonary, aortic, iliac, femoral, and popliteal arteries are most
    commonly involved; cerebral and renal arteries are uncommonly involved [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/32\">",
    " 32",
    " </a>",
    " ]. Acute myocardial infarction can occur due to coronary artery vasculitis
    but is uncommon. Atherosclerosis does not appear to occur at an accelerated rate in
    Beh&ccedil;et&rsquo;s disease, as has been observed in autoimmune diseases such as
    systemic lupus erythematosus [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/15\">",
    " 15",
    " </a>",
    " ].",
    " <br/>",
    " <br/>",
    " Pulmonary arterial involvement is particularly characteristic, and early
    recognition is important. Hemoptysis is the most common presenting symptom; cough,
    dyspnea, fever, and pleuritic pain are other presenting symptoms [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/51,52\">",
    " 51,52",
    " </a>",
    " ]. Pulmonary artery aneurysms involving the large proximal branches of the
    pulmonary arteries are the most common pulmonary vascular lesion in
    Beh&ccedil;et&rsquo;s and are uncommonly seen in diseases other than
    Beh&ccedil;et&rsquo;s. A misdiagnosis of pulmonary embolism and subsequent
    anticoagulation can lead to a poor outcome if the underlying inflammatory large
    vessel vasculitis is not appreciated [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/51\">",
    " 51",
    " </a>",
    " ]. Ventilation-perfusion scans can be misleading; pulmonary arteriography,
    however, is diagnostic. Pulmonary infarction does not commonly occur. Hemoptysis
    may be the result of pulmonary artery-bronchus fistulae and frequently coexists
    with venous obstruction elsewhere [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/14\">",
    " 14",
    " </a>",
    " ].",
    " <br/>",
    " <br/>",
    " Pulmonary artery thrombosis and aneurysms in association with peripheral
    thrombophlebitis are known as Hughes-Stovin syndrome, and this syndrome most
    commonly occurs in Beh&ccedil;et&rsquo;s disease and may represent a part of the
    spectrum of manifestations seen in Beh&ccedil;et&rsquo;s [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/53,54\">",
    " 53,54",
    " </a>",
    " ]. Pulmonary artery thrombosis may occur with pulmonary artery aneurysms or
    may occur independently; a study of 47 patients with pulmonary artery disease and
    Beh&ccedil;et&rsquo;s identified 26 patients with pulmonary artery aneurysms, 13
    with pulmonary artery thrombosis, and eight with both. Presenting manifestations
    were similar. Most patients had active Beh&ccedil;et&rsquo;s at presentation, 85
    percent had pulmonary nodules, 13 percent had cavitation, and 77 percent had
    peripheral venous thrombosis [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/52\">",
    " 52",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Venous disease is more common that arterial. Superior and inferior vena cava
    occlusion, Budd-Chiari syndrome, dural sinus thrombosis, and other venous
    obstructive lesions can occur in addition to the more common superficial and deep
    vein thrombosis. Venous thrombosis is often an early feature of
    Beh&ccedil;et&rsquo;s. Recurrent thrombosis of the lower extremities may lead to a
    post-thrombophlebitic syndrome [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/32\">",
    " 32",
    " </a>",
    " ].",
    " <br/>",
    " <br/>",
    " In one study of 493 cases of Beh&ccedil;et&rsquo;s disease, 53 were found to
    have one or more large vessel thrombosis [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/55\">",
    " 55",
    " </a>",
    " ]. Fourteen of these 53 patients had hepatic vein thrombosis, 8 also had
    inferior vena cava thrombosis, and 2 had both inferior vena cava and portal vein
    thrombosis. A case-control study of 73 Beh&ccedil;et&rsquo;s patients found a 14-
    fold increased risk of venous thrombosis compared with controls [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/56\">",
    " 56",
    " </a>",
    " ]. Venous thrombosis, thrombophlebitis, folliculitis, and retinal vasculitis
    were more common in men than in women. Venous disease may also be more common in
    patients with a positive pathergy test or ocular involvement.",
    " <br/>",
    " <br/>",
    " A study of 2319 Turkish patients with Beh&ccedil;et&rsquo;s found a
    prevalence of vascular disease of 14.3 percent and was most common in males. In
    this study, 53.3 percent suffered superficial venous thrombosis, 29.8 percent deep
    venous thrombosis, and 3.6 percent arterial disease [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/57\">",
    " 57",
    " </a>",
    " ].",
    " <br/>",
    " <br/>",
    " A vascular pathergy-like response may be evident after vascular procedures,
    resulting in phlebitis or aneurysms [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/58,59\">",
    " 58,59",
    " </a>",
    " ].",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H9\">",
    " <span class=\"h2\">",
    " Arthritis",
    " </span>",
    " &nbsp;&mdash;&nbsp;A nonerosive, asymmetric, usually nondeforming arthritis
    occurs in about one-half of patients with Beh&ccedil;et&rsquo;s disease,
    particularly during exacerbations. The arthritis most commonly affects the medium
    and large joints, including the knee, ankle, and wrist. Inflammation is evident on
    synovial fluid and biopsy specimens [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/60\">",
    " 60",
    " </a>",
    " ]. In many patients, the arthritis is intermittent, lasting one to three
    weeks, though manifestations may be persistent. As an example, in a study of Greek
    patients, the arthritis was pauciarticular in about two-thirds, monoarticular in
    about one-third, and polyarticular in less than 5 percent [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/20\">",
    " 20",
    " </a>",
    " ]. Sacroiliitis may occur, particularly in patients with HLA-B27, but in some
    studies is no more likely than in patients without Beh&ccedil;et&rsquo;s [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/61\">",
    " 61",
    " </a>",
    " ]. Despite its nonerosive and nondeforming character, one study using the
    multidimensional Health Assessment Questionnaire showed that arthritis was
    associated with overall functional impairment and pain similar to that seen in
    patients with rheumatoid arthritis [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/62\">",
    " 62",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H10\">",
    " <span class=\"h2\">",
    " Renal disease",
    " </span>",
    " &nbsp;&mdash;&nbsp;Renal involvement in Beh&ccedil;et&rsquo;s disease is less
    frequent and often less severe than in other types of vasculitis. Patients with
    renal disease may have proteinuria, hematuria, or mild renal insufficiency but can
    progress to renal failure.",
    " </p>",
    " <p>",
    " The spectrum of renal diseases associated was illustrated in a review of 159
    patients with renal Beh&ccedil;et&rsquo;s disease: AA (secondary) amyloidosis was
    present in 69, glomerulonephritis in 51, vascular disease (mostly renal arterial
    aneurysms) in 35, and interstitial nephritis in 4 [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/63\">",
    " 63",
    " </a>",
    " ]. Among the patients with glomerulonephritis, there was a spectrum of lesions
    ranging from IgA nephropathy to crescentic glomerulonephritis.",
    " </p>",
    " <p>",
    " Patients with AA amyloidosis typically present with nephrotic syndrome or at
    least significant proteinuria. In a series of 14 cases, the mean time from
    Beh&ccedil;et&rsquo;s onset to amyloid nephropathy was eight years (range 3 to 15
    years) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/64\">",
    " 64",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H11\">",
    " <span class=\"h2\">",
    " Cardiac disease",
    " </span>",
    " &nbsp;&mdash;&nbsp;Symptomatic cardiac disease is uncommon in
    Beh&ccedil;et&rsquo;s disease. Abnormalities that can occur include pericarditis,
    myocarditis, coronary arteritis with or without myocardial infarction, coronary
    artery aneurysms, atrial septal aneurysm, conduction system disturbances,
    ventricular arrhythmias, endocarditis, endomyocardial fibrosis, mitral valve
    prolapse, intracardiac thrombosis, and valvular insufficiency [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/65-68\">",
    " 65-68",
    " </a>",
    " ]. Atherosclerosis does not appear to occur at an accelerated rate as has been
    observed in autoimmune diseases such as systemic lupus erythematosus [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/15\">",
    " 15",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H12\">",
    " <span class=\"h2\">",
    " Gastrointestinal ulcerations",
    " </span>",
    " &nbsp;&mdash;&nbsp;Patients may experience anorexia, nausea, abdominal pain,
    or diarrhea. Gastrointestinal ulcerations occur in some patients with
    Beh&ccedil;et&rsquo;s disease, and intestinal perforation can occur. Discrete
    ulcerations are most often seen in the terminal ileum, cecum, and ascending colon.
    Oral ulcers frequently occur in patients with inflammatory bowel disease that are
    indistinguishable from the oral aphthae of Beh&ccedil;et&rsquo;s disease; thus,
    inflammatory bowel disease needs to be considered before making the diagnosis of
    Beh&ccedil;et&rsquo;s disease. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?24/24/24968?
    source=see_link\">",
    " \"Gastrointestinal manifestations of vasculitis\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H13\">",
    " <span class=\"h2\">",
    " Pulmonary disease",
    " </span>",
    " &nbsp;&mdash;&nbsp;In addition to pulmonary vascular lesions, already
    discussed (see",
    " <a class=\"local\" href=\"#H8\">",
    " 'Vascular disease'",
    " </a>",
    " above), radiographic abnormalities including loss of lung volume, well-defined
    opacities, and indistinct nodular or reticular shadows have been noted, but only
    rarely has histopathologic correlation been available. Among the various pathologic
    findings are pulmonary infarction, hemorrhage, and both organizing and eosinophilic
    pneumonias [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/69\">",
    " 69",
    " </a>",
    " ]. Miscellaneous other pulmonary findings found in Beh&ccedil;et&rsquo;s
    patients include pleural effusion, pulmonary arteritis or venulitis, bronchial
    stenosis, abscess, obstructive airway disease, chronic bronchitis, and fibrosis [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/51\">",
    " 51",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H14\">",
    " <span class=\"h2\">",
    " Pregnancy",
    " </span>",
    " &nbsp;&mdash;&nbsp;Beh&ccedil;et&rsquo;s disease in pregnancy has only been
    evaluated in a few small studies. A case control study of 31 patients who had 135
    pregnancies reported more remissions than exacerbations during and after pregnancy.
    Complications were higher in the study group than the control group, but neonatal
    outcome was not significantly different in the two groups [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/70\">",
    " 70",
    " </a>",
    " ]. A retrospective analysis of Beh&ccedil;et&rsquo;s disease in 44 pregnancies
    in 28 patients reported remission in 52.3 percent of pregnancies, exacerbation in
    27.3 percent, and no change in the clinical course in 20.4 percent, with three
    spontaneous abortions [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/71\">",
    " 71",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H15\">",
    " <span class=\"h2\">",
    " Other",
    " </span>",
    " &nbsp;&mdash;&nbsp;Patients with Beh&ccedil;et&rsquo;s disease may suffer from
    constitutional symptoms including fever and malaise. Problems with urinary and
    erectile function may be due to neural or vascular disease [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/72\">",
    " 72",
    " </a>",
    " ]. Inner ear involvement may cause tinnitus, deafness, or dizziness [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/73\">",
    " 73",
    " </a>",
    " ]. Amyloidosis may occur [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/64\">",
    " 64",
    " </a>",
    " ]. A possible association with myelodysplasia has been discussed [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/74,75\">",
    " 74,75",
    " </a>",
    " ]. A factitious \"pseudo-Beh&ccedil;et&rsquo;s\" syndrome has also been
    described, with predominant mucocutaneous involvement.",
    " </p>",
    " <p>",
    " Fibromyalgia co-occurs in many patients with Beh&ccedil;et&rsquo;s. A study of
    70 Beh&ccedil;et&rsquo;s patients found that 37.1 percent of patients met the
    American College of Rheumatology criteria for fibromyalgia. Fibromyalgia was
    associated with anxiety and depression but not with Beh&ccedil;et&rsquo;s disease
    activity [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/76\">",
    " 76",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H16\">",
    " <span class=\"h1\">",
    " DIAGNOSIS",
    " </span>",
    " &nbsp;&mdash;&nbsp;There are",
    " <strong>",
    " no",
    " </strong>",
    " pathognomonic laboratory tests in Beh&ccedil;et&rsquo;s disease; as a result,
    the diagnosis is made on the basis of the clinical findings. Markers of
    inflammation such as elevated serum of circulating immune complexes, C-reactive
    protein, and the erythrocyte sedimentation rate may be elevated in patients with
    active disease; however, these findings are nonspecific. A number of biochemical
    alterations have been described in Beh&ccedil;et&rsquo;s, ranging from various
    genetic findings to altered cytokine levels and profiles. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?28/12/28874?
    source=see_link\">",
    " \"Pathogenesis of Beh&ccedil;et&rsquo;s disease\"",
    " </a>",
    " .) In the future, some of these may be useful in diagnosis, but the operating
    characteristics of these findings in making the diagnosis of Beh&ccedil;et&rsquo;s
    have not been clearly enough defined to suggest that these should be measured at
    this time for diagnostic purposes [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/77\">",
    " 77",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Several classification criteria have been developed for Beh&ccedil;et&rsquo;s
    disease. Like other classification criteria, these criteria were developed to
    operationalize the definition of the disease to facilitate further research and
    education and were not developed to diagnose disease in individuals [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/78-80\">",
    " 78-80",
    " </a>",
    " ]. It has been suggested that their accuracy is better in populations with low
    prevalence than in those with high [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/80\">",
    " 80",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " The older O'Duffy criteria required oral aphthae, plus as least two of the
    following: genital aphthae; synovitis; posterior uveitis; pathergy; or
    meningoencephalitis, in the absence of inflammatory bowel disease or other collagen
    vascular disease [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/81\">",
    " 81",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Pathergy is defined by a papule 2 mm or more in size developing 24 to 48 hours
    after oblique insertion of a 20 gauge needle 5 mm into the skin, generally
    performed on the forearm.",
    " </p>",
    " <p>",
    " The International Study Group (ISG) criteria, which we prefer, were published
    in 1990 (",
    " <a class=\"graphic graphic_table graphicRef54762 \" href=\"UTD.htm?
    25/47/26363\">",
    " table 2",
    " </a>",
    " ) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/78\">",
    " 78",
    " </a>",
    " ]. These remain the most widely used and well-accepted criteria among experts
    in Beh&ccedil;et&rsquo;s disease. They require the presence of recurrent oral
    aphthae (at least three times in one year) plus two of the following in the absence
    of other systemic diseases:",
    " </p>",
    " <p>",
    " <ul class=\"bulletCompact-block\">",
    " <li>",
    " Recurrent genital aphthae (aphthous ulceration or scarring)",
    " </li>",
    " <li>",
    " Eye lesions (including anterior or posterior uveitis, cells in vitreous on
    slit lamp examination, or retinal vasculitis observed by an ophthalmologist)",
    " </li>",
    " <li>",
    " Skin lesions (including erythema nodosum, pseudo-vasculitis, papulopustular
    lesions, or acneiform nodules consistent with Beh&ccedil;et&rsquo;s)",
    " </li>",
    " <li>",
    " A positive pathergy test",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " These criteria appear to be relatively sensitive and specific [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/82,83\">",
    " 82,83",
    " </a>",
    " ]. As an example, in one report of 32 clinically diagnosed patients with
    Beh&ccedil;et&rsquo;s disease and 56 controls with other rheumatic diseases, the
    sensitivity and specificity were 95 and 100 percent, respectively [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/82\">",
    " 82",
    " </a>",
    " ]. Crohn's disease, ulcerative colitis, and familial Mediterranean fever share
    some clinical manifestations with Beh&ccedil;et&rsquo;s disease. Including patients
    with these disorders among controls did not lead to substantially different
    sensitivity of specificity of the criteria [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/84\">",
    " 84",
    " </a>",
    " ]. Another set of classification criteria has been proposed that adds
    ileocecal ulcerations, does not absolutely require oral ulcerations, and increases
    the weight attributed to the presence of genital ulcerations [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/85\">",
    " 85",
    " </a>",
    " ]. Pathergy is less common in Northern European and North American patients.
    Thus, it has been suggested that other features might be substituted for pathergy
    in these populations, including aseptic meningoencephalitis, cerebral vasculitis,
    recurrent phlebitis, arteritis, synovitis, or focal bowel ulceration [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/82\">",
    " 82",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " The International Criteria for Beh&ccedil;et&rsquo;s disease (ICBD) were
    developed in 2006 in an effort to improve sensitivity compared with the ISG
    criteria, but they are not widely accepted [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/86\">",
    " 86",
    " </a>",
    " ]. Each of several findings is assigned a point value; the criteria require a
    total of at least three points for diagnosis of Beh&ccedil;et&rsquo;s:",
    " </p>",
    " <p>",
    " <ul class=\"bulletCompact-block\">",
    " <li>",
    " Genital aphthosis &mdash; two points",
    " </li>",
    " <li>",
    " Ocular lesions (anterior uveitis, posterior uveitis, or retinal vasculitis)
    &mdash; two points",
    " </li>",
    " <li>",
    " Oral aphthosis &mdash; one point",
    " </li>",
    " <li>",
    " Skin lesions (pseudofolliculitis or erythema nodosum) &mdash; one point",
    " </li>",
    " <li>",
    " Vascular lesions (superficial phlebitis, deep vein thrombosis, large vein
    thrombosis, arterial thrombosis, or aneurysm) &mdash; one point",
    " </li>",
    " <li>",
    " Pathergy &mdash; one point",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Validation studies have estimated a sensitivity of 87 to 96.5 percent, a
    specificity of 88.9 to 97.3 percent, and an accuracy of 74.2 to 85.5 percent for
    these criteria [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/87\">",
    " 87",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Delay in diagnosis is common in nonendemic areas, and delay in diagnosis
    likely increases morbidity and mortality [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/88,89\">",
    " 88,89",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H17\">",
    " <span class=\"h1\">",
    " DIFFERENTIAL DIAGNOSIS",
    " </span>",
    " &nbsp;&mdash;&nbsp;The differential diagnosis varies with each patient's
    clinical features [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/90\">",
    " 90",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Oral aphthae are present in almost all patients with Beh&ccedil;et&rsquo;s,
    and the differential diagnosis of recurrent oral ulcers includes herpes simplex,
    benign aphthous ulcers, inflammatory bowel disease, Stevens-Johnson syndrome, and
    other systemic rheumatic diseases such as systemic lupus erythematosus. Herpes can
    be ruled out with culture or Tzanck preparation. Dental prosthetics and oral
    hygiene products can cause oral irritation and ulceration. Medications such as",
    " <a class=\"drug drug_general\" href=\"UTD.htm?23/38/24170?source=see_link\">",
    " methotrexate",
    " </a>",
    " can cause oral ulcers. Other causes of oral ulcers or stomatitis include
    pemphigoid, pemphigus vulgaris, cicatricial pemphigoid, lichen planus, and linear
    IgA disease. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?25/11/25786?
    source=see_link\">",
    " \"Oral lesions\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Other causes of genital ulceration and an approach to the differential
    diagnosis and evaluation of genital ulcers are discussed in detail elsewhere.
    (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?12/15/12538?
    source=see_link\">",
    " \"Approach to the patient with genital ulcers\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Many other disorders may be associated with the presence of small vessel
    cutaneous vasculitis, inflammatory eye disease, neurologic disease, vascular
    disease, arthritis, or unexplained systemic illness. These include systemic lupus
    erythematosus, inflammatory bowel disease, sarcoidosis, reactive arthritis,
    psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis,
    familial Mediterranean fever and other periodic febrile syndromes, other
    vasculitides, multiple sclerosis, systemic infections such as tuberculosis, human
    immunodeficiency virus, syphilis, and malignancies. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?36/23/37241?
    source=see_link\">",
    " \"Classification of and approach to the vasculitides in adults\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?23/16/23817?
    source=see_link\">",
    " \"Uveitis: Etiology, clinical manifestations, and diagnosis\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?33/15/34039?
    source=see_link\">",
    " \"Evaluation of the adult with polyarticular pain\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H18\">",
    " <span class=\"h1\">",
    " PROGNOSIS",
    " </span>",
    " &nbsp;&mdash;&nbsp;Beh&ccedil;et&rsquo;s disease typically has a waxing and
    waning course characterized by exacerbations and remissions. The disease appears to
    be more severe in young, male, and Middle Eastern or Far Eastern patients [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/15,16\">",
    " 15,16",
    " </a>",
    " ]. In a series of 2200 patients followed at a specialty clinic in Korea, only
    seven died from Beh&ccedil;et&rsquo;s disease over a nine year period [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/91\">",
    " 91",
    " </a>",
    " ]. The mortality in a cohort of 817 patients in France was 5 percent at a
    median follow-up of 7.7 years [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/92\">",
    " 92",
    " </a>",
    " ]. The greatest morbidity and mortality comes from neurologic, ocular, and
    large vessel arterial or venous disease (causing pulmonary disease,
    gastrointestinal bleeding, bowel perforation, superior and inferior vena cava
    syndrome, and cerebrovascular disease). In a 20 year follow-up of 387 Turkish
    patients with Beh&ccedil;et&rsquo;s disease, most were doing better at 20 years,
    with decreased activity of most manifestations other than central nervous system
    involvement and major vessel disease; the latter manifestations may have their
    onset after 5 to 10 years of disease [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/15\">",
    " 15",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Mucocutaneous, articular, and ocular disease are often at their worst in the
    early years of disease, but central nervous system and large vessel disease, if
    they develop, typically do so later in the disease course. Though disease activity
    may decline with passing years, disease burden may rise due to cumulative ocular,
    neurologic or vascular damage. Pulmonary artery aneurysms and associated hemoptysis
    were previously associated with a very poor prognosis, but survival appears to have
    improved, possibly as the result of earlier recognition and treatment using
    glucocorticoids and other immunosuppressive agents. This was illustrated in a
    retrospective study of 26 patients followed at one center in Turkey [",
    " <a class=\"abstract\" href=\"UTD.htm?0/18/298/abstract/93\">",
    " 93",
    " </a>",
    " ]. The five year survival for patients with Beh&ccedil;et&rsquo;s disease and
    pulmonary artery aneurysms who were diagnosed and treated in 1992 or later was 80
    percent versus 40 percent for 24 patients in whom the diagnosis was made prior to
    that year.",
    " </p>",
    " <p>",
    " Ocular and neurologic lesions may improve with immunosuppressive therapy but
    are often not fully reversible. Without aggressive therapy, they generally
    progress. A significant proportion of patients with ocular disease, particularly
    those of Turkish and Japanese descent, suffer progressive vision loss.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"PATIENT_INFORMATION\">",
    " <span class=\"h1\">",
    " INFORMATION FOR PATIENTS",
    " </span>",
    " &nbsp;&mdash;&nbsp;UpToDate offers two types of patient education materials,
    &ldquo;The Basics&rdquo; and &ldquo;Beyond the Basics.&rdquo; The Basics patient
    education pieces are written in plain language, at the 5",
    " <sup>",
    " th",
    " </sup>",
    " to 6",
    " <sup>",
    " th",
    " </sup>",
    " grade reading level, and they answer the four or five key questions a patient
    might have about a given condition. These articles are best for patients who want a
    general overview and who prefer short, easy-to-read materials. Beyond the Basics
    patient education pieces are longer, more sophisticated, and more detailed. These
    articles are written at the 10",
    " <sup>",
    " th",
    " </sup>",
    " to 12",
    " <sup>",
    " th",
    " </sup>",
    " grade reading level and are best for patients who want in-depth information
    and are comfortable with some medical jargon.",
    " </p>",
    " <p>",
    " Here are the patient education articles that are relevant to this topic. We
    encourage you to print or e-mail these topics to your patients. (You can also
    locate patient education articles on a variety of subjects by searching on
    &ldquo;patient info&rdquo; and the keyword(s) of interest.)",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Basics topic (see",
    " <a class=\"medical medical_basics\" href=\"UTD.htm?27/21/27986?
    source=see_link\">",
    " \"Patient information: Beh&ccedil;et&rsquo;s disease (The Basics)\"",
    " </a>",
    " )",
    " </li>",
    " <li>",
    " Beyond the Basics topic (see",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?43/22/44389?
    source=see_link\">",
    " \"Patient information: Vasculitis (Beyond the Basics)\"",
    " </a>",
    " )",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Patient information can also be obtained from The American
    Beh&ccedil;et&rsquo;s Disease Association:",
    " </p>",
    " <p>",
    " The American Beh&ccedil;et&rsquo;s Disease Association",
    " </p>",
    " <p>",
    " PO Box 19952",
    " </p>",
    " <p>",
    " Amarillo, Texas 79114",
    " </p>",
    " <p>",
    " Telephone: 1-800-7BEHCET",
    " </p>",
    " <p>",
    " <a class=\"external\" href=\"file://www.behcets.com/\">",
    " www.Behcets.com",
    " </a>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H4422189\">",
    " <span class=\"h1\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </span>",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Beh&ccedil;et&rsquo;s disease is a rare disease characterized by recurrent
    oral aphthae and any of several systemic manifestations including genital aphthae,
    ocular disease, skin lesions, gastrointestinal disease, neurologic disease,
    vascular disease, and arthritis. Most clinical manifestations of
    Beh&ccedil;et&rsquo;s disease are believed to be due to vasculitis.",
    " </li>",
    " <li>",
    " Beh&ccedil;et&rsquo;s disease is more common (and often more severe) along
    the ancient silk road, which extends from eastern Asia to the Mediterranean; it is
    most common in Turkey, while the prevalence is much lower in North America and
    northern Europe. It typically affects young adults 20 to 40 years of age. (See",
    " <a class=\"local\" href=\"#H591878\">",
    " 'Epidemiology'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " The common clinical feature in patients with Beh&ccedil;et&rsquo;s disease
    is the presence of recurrent and usually painful mucocutaneous ulcers. Other
    clinical manifestations of this disorder are more variable among different patients
    and populations. (See",
    " <a class=\"local\" href=\"#H2\">",
    " 'Clinical manifestations'",
    " </a>",
    " above and",
    " <a class=\"local\" href=\"#H3\">",
    " 'Oral ulcerations'",
    " </a>",
    " above and",
    " <a class=\"local\" href=\"#H4\">",
    " 'Urogenital lesions'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " The greatest morbidity and mortality occur with ocular disease (affecting up
    to two-thirds of patients), including uveitis and other changes; with vascular
    disease (affecting up to one-third of patients), most commonly a small vessel
    vasculitis; and with central nervous system disease (affecting 10 to 20 percent of
    patients), including focal parenchymal lesions, complications of vascular
    thrombosis, and other abnormalities. Vasculitis in patients with
    Beh&ccedil;et&rsquo;s disease is remarkable for its ability to involve blood
    vessels of all sizes and to involve both arteries and veins. (See",
    " <a class=\"local\" href=\"#H8\">",
    " 'Vascular disease'",
    " </a>",
    " above and",
    " <a class=\"local\" href=\"#H6\">",
    " 'Ocular disease'",
    " </a>",
    " above and",
    " <a class=\"local\" href=\"#H7\">",
    " 'Neurologic disease'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Cutaneous and articular manifestations are common, which included acne,
    folliculitis, and erythema nodosum lesions. Pathergy may be seen as an erythematous
    papular or pustular response to local skin injury. The arthritis is
    characteristically intermittent, inflammatory but nonerosive, asymmetric, and,
    usually, nondeforming; it often occurs during disease exacerbations and most
    commonly affects the medium and large joints. A variety of gastrointestinal (GI)
    symptoms may occur. (See",
    " <a class=\"local\" href=\"#H5\">",
    " 'Cutaneous lesions'",
    " </a>",
    " above and",
    " <a class=\"local\" href=\"#H9\">",
    " 'Arthritis'",
    " </a>",
    " above and",
    " <a class=\"local\" href=\"#H12\">",
    " 'Gastrointestinal ulcerations'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Less common manifestations include renal disease and peripheral nervous
    system involvement. Cardiac and pulmonary disease may also be present. (See",
    " <a class=\"local\" href=\"#H10\">",
    " 'Renal disease'",
    " </a>",
    " above and",
    " <a class=\"local\" href=\"#H7\">",
    " 'Neurologic disease'",
    " </a>",
    " above and",
    " <a class=\"local\" href=\"#H11\">",
    " 'Cardiac disease'",
    " </a>",
    " above and",
    " <a class=\"local\" href=\"#H13\">",
    " 'Pulmonary disease'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " There are no pathognomonic laboratory tests in Beh&ccedil;et&rsquo;s
    disease; the diagnosis is made on the basis of the clinical findings. Nonspecific
    elevation of acute phase reactants is often seen. (See",
    " <a class=\"local\" href=\"#H16\">",
    " 'Diagnosis'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " International criteria have relatively high sensitivity and specificity.
    They require the presence of recurrent oral aphthae (three times in one year) plus
    two of the following in the absence of other systemic diseases (",
    " <a class=\"graphic graphic_table graphicRef54762 \" href=\"UTD.htm?
    25/47/26363\">",
    " table 2",
    " </a>",
    " ) (see",
    " <a class=\"local\" href=\"#H16\">",
    " 'Diagnosis'",
    " </a>",
    " above):",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " <ul class=\"hyphen-block\">",
    " <li>",
    " Recurrent genital aphthae",
    " </li>",
    " <li>",
    " Eye lesions (including anterior or posterior uveitis, cells in vitreous on
    slit lamp examination, or retinal vasculitis observed by an ophthalmologist)",
    " </li>",
    " <li>",
    " Skin lesions (including erythema nodosum, pseudo-vasculitis, papulopustular
    lesions, or acneiform nodules consistent with Beh&ccedil;et&rsquo;s)",
    " </li>",
    " <li>",
    " A positive pathergy test",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Beh&ccedil;et&rsquo;s disease typically has a waxing and waning course
    characterized by exacerbations and remissions. The disease appears to be more
    severe in young, male, and Middle Eastern or Far Eastern patients. The greatest
    morbidity and mortality comes from neurologic, ocular, and large-vessel arterial or
    venous disease. Mucocutaneous, articular, and ocular diseases are often at their
    worst in the early years of disease, but central nervous system and large-vessel
    diseases, if they develop, may do so later in the disease course. (See",
    " <a class=\"local\" href=\"#H18\">",
    " 'Prognosis'",
    " </a>",
    " above.)",
    " </li>",
    " </ul>",
    " </p>",
    " </div>",
    " <div id=\"topicAgreement\">",
    " Use of UpToDate is subject to the",
    " <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
    target=\"_blank\">",
    " Subscription and License Agreement",
    " </a>",
    " .",
    " </div>",
    " <div class=\"headingAnchor\" id=\"references\">",
    " <h1>",
    " REFERENCES",
    " </h1>",
    " <ol id=\"reference\">",
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    " Yazici H, Ba��aran G, Hamuryudan V, et al. The ten-year mortality in
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/18\">",
    " Kon&eacute;-Paut I, Geisler I, Wechsler B, et al. Familial aggregation in
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    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/19\">",
    " G&uuml;lbay B, Acican T, Er&ccedil;en Diken &Ouml;, Pinar &Ouml;nen Z.
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    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/20\">",
    " Zouboulis CC, Vaiopoulos G, Marcomichelakis N, et al. Onset signs, clinical
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    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/21\">",
    " Uluduz D, K&uuml;rt&uuml;nc&uuml; M, Yap��c�� Z, et al. Clinical
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/22\">",
    " Soy M, Erken E, Konca K, Ozbek S. Smoking and Beh&ccedil;et's disease. Clin
    Rheumatol 2000; 19:508.",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/23\">",
    " Kaklamani VG, Vaiopoulos G, Markomichelakis N, Kaklamanis P. Recurrent
    epididymo-orchitis in patients with Beh&ccedil;et's disease. J Urol 2000;
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    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/24\">",
    " Cho YH, Jung J, Lee KH, et al. Clinical features of patients with
    Beh&ccedil;et's disease and epididymitis. J Urol 2003; 170:1231.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/25\">",
    " Demirkesen C, T&uuml;z&uuml;ner N, Mat C, et al. Clinicopathologic
    evaluation of nodular cutaneous lesions of Beh&ccedil;et syndrome. Am J Clin Pathol
    2001; 116:341.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/26\">",
    " Diri E, Mat C, Hamuryudan V, et al. Papulopustular skin lesions are seen
    more frequently in patients with Beh&ccedil;et's syndrome who have arthritis: a
    controlled and masked study. Ann Rheum Dis 2001; 60:1074.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/27\">",
    " Tunc R, Keyman E, Melikoglu M, et al. Target organ associations in Turkish
    patients with Beh&ccedil;et's disease: a cross sectional study by exploratory
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    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/28\">",
    " Hatemi G, Bahar H, Uysal S, et al. The pustular skin lesions in Behcet's
    syndrome are not sterile. Ann Rheum Dis 2004; 63:1450.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/29\">",
    " Din&ccedil; A, Karaayvaz M, Caliskaner AZ, et al. Dermographism and atopy in
    patients with Beh&ccedil;et's disease. J Investig Allergol Clin Immunol 2000;
    10:368.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/30\">",
    " Vaiopoulos G, Pangratis N, Samarkos M, et al. Nailfold capillary
    abnormalities in Beh&ccedil;et's disease. J Rheumatol 1995; 22:1108.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/31\">",
    " Nussenblatt RB. Uveitis in Beh&ccedil;et's disease. Int Rev Immunol 1997;
    14:67.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/32\">",
    " Seyahi E, Melikoglu M, Yazici H. Clinical features and diagnosis of Behcet's
    syndrome. Int J Adv Rheumatol 2007; 5:8.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/33\">",
    " Matsuo T, Itami M, Nakagawa H, Nagayama M. The incidence and pathology of
    conjunctival ulceration in Beh&ccedil;et's syndrome. Br J Ophthalmol 2002;
    86:140.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/34\">",
    " Zamir E, Bodaghi B, Tugal-Tutkun I, et al. Conjunctival ulcers in
    Beh&ccedil;et's disease. Ophthalmology 2003; 110:1137.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/35\">",
    " Tugal-Tutkun I, Onal S, Altan-Yaycioglu R, et al. Neovascularization of the
    optic disc in Beh&ccedil;et's disease. Jpn J Ophthalmol 2006; 50:256.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/36\">",
    " Tugal-Tutkun I, Onal S, Altan-Yaycioglu R, et al. Uveitis in Beh&ccedil;et
    disease: an analysis of 880 patients. Am J Ophthalmol 2004; 138:373.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/37\">",
    " Akman-Demir G, Serdaroglu P, Tas&ccedil;i B. Clinical patterns of
    neurological involvement in Beh&ccedil;et's disease: evaluation of 200 patients.
    The Neuro-Beh&ccedil;et Study Group. Brain 1999; 122 ( Pt 11):2171.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/38\">",
    " Serdaro��lu P. Beh&ccedil;et's disease and the nervous system. J Neurol
    1998; 245:197.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/39\">",
    " Siva A, Saip S. The spectrum of nervous system involvement in
    Beh&ccedil;et's syndrome and its differential diagnosis. J Neurol 2009; 256:513.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/40\">",
    " Al-Araji A, Kidd DP. Neuro-Beh&ccedil;et's disease: epidemiology, clinical
    characteristics, and management. Lancet Neurol 2009; 8:192.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/41\">",
    " Atasoy HT, Tunc TO, Unal AE, et al. Peripheral nervous system involvement in
    patients with Beh&ccedil;et disease. Neurologist 2007; 13:225.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/42\">",
    " Akbulut L, Gur G, Bodur H, et al. Peripheral neuropathy in Beh&ccedil;et
    disease: an electroneurophysiological study. Clin Rheumatol 2007; 26:1240.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/43\">",
    " Benamour S, Naji T, Alaoui FZ, et al. [Neurological involvement in
    Beh&ccedil;et's disease. 154 cases from a cohort of 925 patients and review of the
    literature]. Rev Neurol (Paris) 2006; 162:1084.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/44\">",
    " Lee SH, Yoon PH, Park SJ, Kim DI. MRI findings in neuro-beh&ccedil;et's
    disease. Clin Radiol 2001; 56:485.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/45\">",
    " Farah S, Al-Shubaili A, Montaser A, et al. Beh&ccedil;et's syndrome: a
    report of 41 patients with emphasis on neurological manifestations. J Neurol
    Neurosurg Psychiatry 1998; 64:382.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/46\">",
    " Allen NB. Miscellaneous vasculitic syndromes including Beh&ccedil;et's
    disease and central nervous system vasculitis. Curr Opin Rheumatol 1993; 5:51.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/47\">",
    " Saadoun D, Wechsler B, Resche-Rigon M, et al. Cerebral venous thrombosis in
    Beh&ccedil;et's disease. Arthritis Rheum 2009; 61:518.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/48\">",
    " Kidd D, Steuer A, Denman AM, Rudge P. Neurological complications in
    Beh&ccedil;et's syndrome. Brain 1999; 122 ( Pt 11):2183.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/49\">",
    " Ko&ccedil; Y, G&uuml;ll&uuml; I, Akpek G, et al. Vascular involvement in
    Beh&ccedil;et's disease. J Rheumatol 1992; 19:402.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/50\">",
    " Calamia KT, Schirmer M, Melikoglu M. Major vessel involvement in
    Beh&ccedil;et disease. Curr Opin Rheumatol 2005; 17:1.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/51\">",
    " Uzun O, Akpolat T, Erkan L. Pulmonary vasculitis in behcet disease: a
    cumulative analysis. Chest 2005; 127:2243.",
    " </a>",
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    " Seyahi E, Melikoglu M, Akman C, et al. Pulmonary artery involvement and
    associated lung disease in Beh&ccedil;et disease: a series of 47 patients. Medicine
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/53\">",
    " Hamuryudan V, Oz B, T&uuml;z&uuml;n H, Yazici H. The menacing pulmonary
    artery aneurysms of Beh&ccedil;et's syndrome. Clin Exp Rheumatol 2004; 22:S1.",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/54\">",
    " Erkan D, Yazici Y, Sanders A, et al. Is Hughes-Stovin syndrome
    Beh&ccedil;et's disease? Clin Exp Rheumatol 2004; 22:S64.",
    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/55\">",
    " Bayraktar Y, Balkanci F, Bayraktar M, Calguneri M. Budd-Chiari syndrome: a
    common complication of Beh&ccedil;et's disease. Am J Gastroenterol 1997; 92:858.",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/56\">",
    " Ames PR, Steuer A, Pap A, Denman AM. Thrombosis in Beh&ccedil;et's disease:
    a retrospective survey from a single UK centre. Rheumatology (Oxford) 2001;
    40:652.",
    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/57\">",
    " Sarica-Kucukoglu R, Akdag-Kose A, KayabalI M, et al. Vascular involvement in
    Beh&ccedil;et's disease: a retrospective analysis of 2319 cases. Int J Dermatol
    2006; 45:919.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/58\">",
    " L&ecirc; Thi Huong D, Wechsler B, Papo T, et al. Arterial lesions in
    Beh&ccedil;et's disease. A study in 25 patients. J Rheumatol 1995; 22:2103.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/59\">",
    " O'Duffy JD. Vasculitis in Beh&ccedil;et's disease. Rheum Dis Clin North Am
    1990; 16:423.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/60\">",
    " Kim HA, Choi KW, Song YW. Arthropathy in Beh&ccedil;et's disease. Scand J
    Rheumatol 1997; 26:125.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/61\">",
    " Maghraoui AE, Tabache F, Bezza A, et al. A controlled study of sacroiliitis
    in Beh&ccedil;et's disease. Clin Rheumatol 2001; 20:189.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/62\">",
    " Moses Alder N, Fisher M, Yazici Y. Beh&ccedil;et's syndrome patients have
    high levels of functional disability, fatigue and pain as measured by a Multi-
    dimensional Health Assessment Questionnaire (MDHAQ). Clin Exp Rheumatol 2008;
    26:S110.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/63\">",
    " Akpolat T, Akkoyunlu M, Akpolat I, et al. Renal Beh&ccedil;et's disease: a
    cumulative analysis. Semin Arthritis Rheum 2002; 31:317.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/64\">",
    " Meliko��lu M, Altiparmak MR, Fresko I, et al. A reappraisal of amyloidosis
    in Beh&ccedil;et's syndrome. Rheumatology (Oxford) 2001; 40:212.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/65\">",
    " G&ouml;ldeli O, Ural D, Komsuo��lu B, et al. Abnormal QT dispersion in
    Beh&ccedil;et's disease. Int J Cardiol 1997; 61:55.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/66\">",
    " Huong DL, Wechsler B, Papo T, et al. Endomyocardial fibrosis in
    Beh&ccedil;et's disease. Ann Rheum Dis 1997; 56:205.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/67\">",
    " G&uuml;rg&uuml;n C, Ercan E, Ceyhan C, et al. Cardiovascular involvement in
    Beh&ccedil;et's disease. Jpn Heart J 2002; 43:389.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/68\">",
    " Geri G, Wechsler B, Thi Huong du L, et al. Spectrum of cardiac lesions in
    Beh&ccedil;et disease: a series of 52 patients and review of the literature.
    Medicine (Baltimore) 2012; 91:25.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/69\">",
    " Uzun O, Erkan L, Akpolat I, et al. Pulmonary involvement in Beh&ccedil;et's
    disease. Respiration 2008; 75:310.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/70\">",
    " Jadaon J, Shushan A, Ezra Y, et al. Beh&ccedil;et's disease and pregnancy.
    Acta Obstet Gynecol Scand 2005; 84:939.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/71\">",
    " Uzun S, Alpsoy E, Durdu M, Akman A. The clinical course of Beh&ccedil;et's
    disease in pregnancy: a retrospective analysis and review of the literature. J
    Dermatol 2003; 30:499.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/72\">",
    " Erdo��ru T, Ko&ccedil;ak T, Serdaro��lu P, et al. Evaluation and therapeutic
    approaches of voiding and erectile dysfunction in neurological Beh&ccedil;et's
    syndrome. J Urol 1999; 162:147.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/73\">",
    " Choung YH, Cho MJ, Park K, et al. Audio-vestibular disturbance in patients
    with Beh&ccedil;et's disease. Laryngoscope 2006; 116:1987.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/74\">",
    " Tada Y, Koarada S, Haruta Y, et al. The association of Beh&ccedil;et's
    disease with myelodysplastic syndrome in Japan: a review of the literature. Clin
    Exp Rheumatol 2006; 24:S115.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/75\">",
    " Arimura K, Arima N, Matsushita K, et al. High incidence of morphological
    myelodysplasia and apoptotic bone marrow cells in Beh&ccedil;et's disease. J Clin
    Immunol 2007; 27:145.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/76\">",
    " Lee SS, Yoon HJ, Chang HK, Park KS. Fibromyalgia in Beh&ccedil;et's disease
    is associated with anxiety and depression, and not with disease activity. Clin Exp
    Rheumatol 2005; 23:S15.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/77\">",
    " Saglam K, Yilmaz MI, Saglam A, et al. Levels of circulating intercellular
    adhesion molecule-1 in patients with Beh&ccedil;et's disease. Rheumatol Int 2002;
    21:146.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/78\">",
    " Criteria for diagnosis of Beh&ccedil;et's disease. International Study Group
    for Beh&ccedil;et's Disease. Lancet 1990; 335:1078.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/79\">",
    " Smith EL, Shmerling RH. The American College of Rheumatology criteria for
    the classification of systemic lupus erythematosus: strengths, weaknesses, and
    opportunities for improvement. Lupus 1999; 8:586.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/80\">",
    " Dinc A, Bayir A, Simsek I, et al. The proportional Venn diagram of
    Beh&ccedil;et's disease-related manifestations among young adult men in Turkey.
    Clin Exp Rheumatol 2005; 23:S86.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/81\">",
    " O'Duffy JD. Suggested criteria for diagnosis of Behcet's disease (abstract).
    J Rheumatol 1974; 1(Suppl 1):18.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/82\">",
    " Ferraz MB, Walter SD, Heymann R, Atra E. Sensitivity and specificity of
    different diagnostic criteria for Beh&ccedil;et's disease according to the latent
    class approach. Br J Rheumatol 1995; 34:932.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/83\">",
    " O'Neill TW, Rigby AS, Silman AJ, Barnes C. Validation of the International
    Study Group criteria for Beh&ccedil;et's disease. Br J Rheumatol 1994; 33:115.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/84\">",
    " Tun&ccedil; R, Uluhan A, Meliko��lu M, et al. A reassessment of the
    International Study Group criteria for the diagnosis (classification) of
    Beh&ccedil;et's syndrome. Clin Exp Rheumatol 2001; 19:S45.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/85\">",
    " Chang HK, Lee SS, Bai HJ, et al. Validation of the classification criteria
    commonly used in Korea and a modified set of preliminary criteria for
    Beh&ccedil;et's disease: a multi-center study. Clin Exp Rheumatol 2004; 22:S21.",
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    " </li>",
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    " Davatchi F, Schirmer M, Zouboulis C, et al, on behalf of the International
    Team for the Revision of the International Study Group Criteria for Bechet's
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/87\">",
    " Davatchi F. Diagnosis/Classification Criteria for Behcet's Disease. Patholog
    Res Int 2012; 2012:607921.",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/88\">",
    " Alpsoy E. Beh&ccedil;et's disease: treatment of mucocutaneous lesions. Clin
    Exp Rheumatol 2005; 23:532.",
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    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/89\">",
    " Yazici H, T&uuml;z&uuml;n Y, Pazarli H, et al. Influence of age of onset and
    patient's sex on the prevalence and severity of manifestations of Beh&ccedil;et's
    syndrome. Ann Rheum Dis 1984; 43:783.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/90\">",
    " Barnes CG, Yazici H. Beh&ccedil;et's syndrome. Rheumatology (Oxford) 1999;
    38:1171.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/91\">",
    " Park KD, Bang D, Lee ES, et al. Clinical study on death in Beh&ccedil;et's
    disease. J Korean Med Sci 1993; 8:241.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/92\">",
    " Saadoun D, Wechsler B, Desseaux K, et al. Mortality in Beh&ccedil;et's
    disease. Arthritis Rheum 2010; 62:2806.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/18/298/abstract/93\">",
    " Hamuryudan V, Er T, Seyahi E, et al. Pulmonary artery aneurysms in
    Beh&ccedil;et syndrome. Am J Med 2004; 117:867.",
    " </a>",
    " </li>",
    " </ol>",
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    " </a>",
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    " <div id=\"innerOutline\">",
    " <h1>",
    " TOPIC OUTLINE",
    " </h1>",
    " <div id=\"outline\">",
    " <ul>",
    " <li>",
    " <a class=\"sr_button\" href=\"#H4422189\" id=\"summRecButton\">",
    " <span>",
    " SUMMARY &amp; RECOMMENDATIONS",
    " </span>",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H1\">",
    " INTRODUCTION",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H591878\">",
    " EPIDEMIOLOGY",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H2\">",
    " CLINICAL MANIFESTATIONS",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H3\">",
    " Oral ulcerations",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H4\">",
    " Urogenital lesions",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H5\">",
    " Cutaneous lesions",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H6\">",
    " Ocular disease",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H7\">",
    " Neurologic disease",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H8\">",
    " Vascular disease",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H9\">",
    " Arthritis",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H10\">",
    " Renal disease",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H11\">",
    " Cardiac disease",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H12\">",
    " Gastrointestinal ulcerations",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H13\">",
    " Pulmonary disease",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H14\">",
    " Pregnancy",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H15\">",
    " Other",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H16\">",
    " DIAGNOSIS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H17\">",
    " DIFFERENTIAL DIAGNOSIS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H18\">",
    " PROGNOSIS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#PATIENT_INFORMATION\">",
    " INFORMATION FOR PATIENTS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H4422189\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " <div class=\"openRelatedGraphics\" id=\"RHEUM/8223\" rel=\"outline_link\">",
    " GRAPHICS",
    " <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
    " View All",
    " </a>",
    " </div>",
    " </h1>",
    " <div id=\"relatedGraphics\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <div class=\"openRelatedGraphics\" id=\"RHEUM/8223|PIC\">",
    " <a href=\"#\" title=\"PICTURES\">",
    " PICTURES",
    " </a>",
    " </div>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_picture\" href=\"UTD.htm?9/62/10222\"
    title=\"picture 1\">",
    " Oral aphthae in Behcets",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_picture\" href=\"UTD.htm?31/47/32497\"
    title=\"picture 2\">",
    " Vasculitic ulcers in Behcets",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_picture\" href=\"UTD.htm?0/58/943\"
    title=\"picture 3A\">",
    " Behcet disease uveitis",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_picture\" href=\"UTD.htm?11/7/11391\"
    title=\"picture 3B\">",
    " Retinal ischemia in Behcets",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <div class=\"openRelatedGraphics\" id=\"RHEUM/8223|TAB\">",
    " <a href=\"#\" title=\"TABLES\">",
    " TABLES",
    " </a>",
    " </div>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?9/6/9324\" title=\"table
    1\">",
    " Vascular disease in Behcets",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?25/47/26363\" title=\"table
    2\">",
    " Diagnosis of Behcets disease",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " RELATED TOPICS",
    " </h1>",
    " <div id=\"relatedTopics\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?12/15/12538?
    source=related_link\">",
    " Approach to the patient with genital ulcers",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?36/23/37241?
    source=related_link\">",
    " Classification of and approach to the vasculitides in adults",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?33/15/34039?
    source=related_link\">",
    " Evaluation of the adult with polyarticular pain",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?24/24/24968?
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    " <a class=\"medical medical_review\" href=\"UTD.htm?25/11/25786?
    source=related_link\">",
    " Oral lesions",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
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    source=related_link\">",
    " Pathogenesis of Beh&ccedil;et&rsquo;s disease",
    " </a>",
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    " <a class=\"medical medical_basics\" href=\"UTD.htm?27/21/27986?
    source=related_link\">",
    " Patient information: Beh&ccedil;et&rsquo;s disease (The Basics)",
    " </a>",
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    " <li class=\"plainItem\">",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?43/22/44389?
    source=related_link\">",
    " Patient information: Vasculitis (Beyond the Basics)",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?32/45/33498?
    source=related_link\">",
    " Treatment of Beh&ccedil;et&rsquo;s disease",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?23/16/23817?
    source=related_link\">",
    " Uveitis: Etiology, clinical manifestations, and diagnosis",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " </div>"].join("\n");
    var title_f0_18_299="Definition of accuracy";
    var content_f0_18_299=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=PC
    %2F55297&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\">",
    " <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
    title=\"Print this page\"/>",
    " </a>",
    " <a class=\"icontxt textLink\" href=\"?imageKey=PC
    %2F55297&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\"
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    " Print",
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    " <a class=\"etacLink\" href=\"#\">",
    " <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
    title=\"Email graphic(s)\"/>",
    " </a>",
    " <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
    " Email",
    " </a>",
    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\">",
    " <div class=\"ttl\">",
    " Definition of accuracy",
    " </div>",
    " <div class=\"cntnt\">",
    " <table cellspacing=\"0\">",
    " <tbody>",
    " <tr>",
    " <td class=\"subtitle1\">",
    " &nbsp;",
    " </td>",
    " <td class=\"subtitle1\">",
    " Disease present",
    " </td>",
    " <td class=\"subtitle1\">",
    " Disease absent",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Test positive",
    " </td>",
    " <td>",
    " A",
    " </td>",
    " <td>",
    " B",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Test negative",
    " </td>",
    " <td>",
    " C",
    " </td>",
    " <td>",
    " D",
    " </td>",
    " </tr>",
    " </tbody>",
    " </table>",
    " </div>",
    " <div class=\"lgnd\">",
    " <div class=\"footnotes\">",
    " Accuracy = the number of true positives plus the number of true negatives
    expressed as a percentage (ie, (A + D)/(A + B + C + D)).",
    " </div>",
    " <div class=\"reference\">",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_18_299=[""].join("\n");
    var outline_f0_18_299=null;
    var title_f0_18_300="Liver tumor study group HCC";
    var content_f0_18_300=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=GAST
    %2F53242&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\">",
    " <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
    title=\"Print this page\"/>",
    " </a>",
    " <a class=\"icontxt textLink\" href=\"?imageKey=GAST
    %2F53242&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\"
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    " Print",
    " </a>",
    " <a class=\"etacLink\" href=\"#\">",
    " <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
    title=\"Email graphic(s)\"/>",
    " </a>",
    " <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
    " Email",
    " </a>",
    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\">",
    " <div class=\"ttl\">",
    " American Liver Tumor Study Group modification of the TNM staging for
    hepatocellular cancer for the purpose of liver transplantation prioritization",
    " </div>",
    " <div class=\"cntnt\">",
    " <table cellspacing=\"0\">",
    " <tbody>",
    " <tr>",
    " <td>",
    " T0",
    " </td>",
    " <td>",
    " No tumor found",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " T1",
    " </td>",
    " <td>",
    " One nodule, &le;1.9 cm",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " T2",
    " </td>",
    " <td>",
    " One nodule, 2 to 5 cm; two or three nodules, all &le;3 cm",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " T3",
    " </td>",
    " <td>",
    " One nodule, &gt;5 cm, two or three nodules at least one &gt;3 cm",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " T4a",
    " </td>",
    " <td>",
    " Four or more nodules of any size",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " T4b",
    " </td>",
    " <td>",
    " T2, T3, or T4a, plus gross involvement of intrahepatic portal vein or
    hepatic vein, as indicated by CT, MRI, or ultrasonography",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " N1",
    " </td>",
    " <td>",
    " Involvement of regional (porta hepatis) lymph nodes",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " M1",
    " </td>",
    " <td>",
    " Metastatic disease including extrahepatic portal or hepatic vein
    involvement",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"subtitle1_single\" colspan=\"2\" rowspan=\"1\">",
    " Stage grouping",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Stage I",
    " </td>",
    " <td>",
    " T1",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Stage II",
    " </td>",
    " <td>",
    " T2",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Stage III",
    " </td>",
    " <td>",
    " T3",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Stage IVA1",
    " </td>",
    " <td>",
    " T4a",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Stage IVA2",
    " </td>",
    " <td>",
    " T4b",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Stage IVB",
    " </td>",
    " <td>",
    " Any N1 or M1",
    " </td>",
    " </tr>",
    " </tbody>",
    " </table>",
    " </div>",
    " <div class=\"lgnd\">",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_18_300=[""].join("\n");
    var outline_f0_18_300=null;
    var title_f0_18_301="Adverse effects antidepress";
    var content_f0_18_301=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=PEDS
    %2F63001&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=12\"
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    title=\"Print this page\"/>",
    " </a>",
    " <a class=\"icontxt textLink\" href=\"?imageKey=PEDS
    %2F63001&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=12\" onclick=\"\"
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    " Print",
    " </a>",
    " <a class=\"etacLink\" href=\"#\">",
    " <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
    title=\"Email graphic(s)\"/>",
    " </a>",
    " <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
    " Email",
    " </a>",
    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\">",
    " <div class=\"ttl\">",
    " Monitoring and addressing adverse responses to starting antidepressants",
    " </div>",
    " <div class=\"cntnt\">",
    " <table cellspacing=\"0\">",
    " <tbody>",
    " <tr>",
    " <td class=\"subtitle1\">",
    " &nbsp;",
    " </td>",
    " <td class=\"subtitle1\">",
    " Suicidality",
    " </td>",
    " <td class=\"subtitle1\">",
    " Akathisia*",
    " </td>",
    " <td class=\"subtitle1\">",
    " Manic switching&bull;",
    " </td>",
    " <td class=\"subtitle1\">",
    " Discontinuation syndrome",
    " </td>",
    " <td class=\"subtitle1\">",
    " Serotonergic syndrome&Delta;",
    " </td>",
    " <td class=\"subtitle1\">",
    " Apathy",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Symptoms",
    " </td>",
    " <td>",
    " Thoughts or acts of self-harm",
    " </td>",
    " <td>",
    " Inner restlessness; sense of being \"driven\": pacing or movements usually
    bilateral, symmetrical, often specific muscle groups",
    " </td>",
    " <td>",
    " Silliness, giggling, angry outbursts, lack of sleep",
    " </td>",
    " <td>",
    " Fear, dizziness, lethargy, parasthesias, nausea, vivid dreams, insomnia,
    increased irritability or depression",
    " </td>",
    " <td>",
    " Confusion, restlessness, agitation, fever, hyperthermia, diaphoresis,
    hypertonia/clonus (usually symmetrical), tremor, shivering, hyper-reflexia",
    " </td>",
    " <td>",
    " Disinterest, confusion, lack of enjoyment in previously enjoyed
    activities; NOT depressed",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Incidence",
    " </td>",
    " <td>",
    " 2 percent",
    " </td>",
    " <td>",
    " 5-25 percent",
    " </td>",
    " <td>",
    " 2-70 percent in bipolar depression, but 1-10 percent in unipolar
    depression (TCA &gt;SSRI)",
    " </td>",
    " <td>",
    " 4-18 percent; shorter half-live antidepressants &gt;longer half-life
    agents",
    " </td>",
    " <td>",
    " Rare (&lt;1 percent)",
    " </td>",
    " <td>",
    " &nbsp;",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " When most commonly occurs",
    " </td>",
    " <td>",
    " 1-4 weeks",
    " </td>",
    " <td>",
    " 2-6 weeks",
    " </td>",
    " <td>",
    " 2-4 weeks, or within weeks of dose increases",
    " </td>",
    " <td>",
    " Within 1-7 days of stopping, decreasing antidepressant",
    " </td>",
    " <td>",
    " When multiple serotonergic medications are added or combined",
    " </td>",
    " <td>",
    " 24-78 weeks",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Response",
    " </td>",
    " <td>",
    " Discontinue, monitor resolution of suicidality, consider alternative
    antidepressant",
    " </td>",
    " <td>",
    " Consider switch to alternative agent; if very positive response for
    depression, consider propanolol, or &lt;4 weeks augmentation with clonazapam",
    " </td>",
    " <td>",
    " Discontinue antidepressant; consider mood stablizers if impairing mania
    (vs milder hypomanic symptoms); after manic symptoms resolve, if prominent
    depression, consider alternative antidepressants, but titrate slowly and attempt
    low doses",
    " </td>",
    " <td>",
    " Resume antidepressant and titrate down slowly; consider switching/adding
    long half-life antidepressant (fluoxetine) to allow more gradual taper",
    " </td>",
    " <td>",
    " Hospital management of hyperthermia, benzodiazepines for seizures or
    muscle hyperactivity; serotonin antagonists such as cyproheptadine 4-8 mg up to
    four times a day",
    " </td>",
    " <td>",
    " Consider augmentation with additional antidepressant, but at low dose (eg,
    bupropion SR 100 mg every morning)",
    " </td>",
    " </tr>",
    " </tbody>",
    " </table>",
    " </div>",
    " <div class=\"lgnd\">",
    " <div class=\"footnotes\">",
    " * Hansek L. A critical review of akathisia, and its possible association with
    suicidal behavior. Hum Psychopharm Clin Exp 2001; 16:495-505.",
    " <br>",
    " &bull; Martin A, Young C, Leckman JF, Mukonoweshuro C, Rosenheck R, Leslie
    D. Age effects on antidepressant-induced manic conversion. Arch Pediatr Adolesc Med
    2004;158:773-780.",
    " <br>",
    " &Delta; Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med
    2005;352:1112-20.",
    " </br>",
    " </br>",
    " </div>",
    " <div class=\"reference\">",
    " Reproduced with permission from: Rappaport, N, Bostic, JQ, Prince JB,
    Jellinek, M. Treating pediatric depression in primary care: Coping with the
    patients' blue mood and the FDA's black box. J Pediatr 2006; 148:567. Copyright
    &copy;2006 Elsevier.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_18_301=[""].join("\n");
    var outline_f0_18_301=null;
    var title_f0_18_302="Seasonal pattern MI";
    var content_f0_18_302=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=CARD
    %2F82538&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\">",
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    " <a class=\"icontxt textLink\" href=\"?imageKey=CARD
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    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\" style=\"width: 501px\">",
    " <div class=\"ttl\">",
    " Incidence of MI is lowest during the summer",
    " </div>",
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    HEjx44eP4IMKXIkyZImTwmiTKlyJctkIQAAOw==);\">",
    " </div>",
    " <div class=\"lgnd\">",
    " Analysis of 259,891 patients hospitalized for an acute myocardial infarction
    (MI) demonstrates a gradual decline in the number of MIs during the spring,
    reaching a nadir in the summer, and an increase during the fall, reaching a maximum
    in the winter. Approximately 53 percent more infarctions occurred in the winter or
    spring compared to the summer.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " Data from Spencer, FA, Goldberg, RJ, Becker, RC, et al, and the Participants
    in the National Registry of Myocardial Infarction, J Am Coll Cardiol 1998;
    31:1226.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_18_302=[""].join("\n");
    var outline_f0_18_302=null;
    var title_f0_18_303="Genes involved DSD A";
    var content_f0_18_303=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=PEDS
    %2F81145&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=2\" onclick=\"\">",
    " <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
    title=\"Print this page\"/>",
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    " <a class=\"icontxt textLink\" href=\"?imageKey=PEDS
    %2F81145&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=2\" onclick=\"\"
    title=\"Print this page\">",
    " Print",
    " </a>",
    " <a class=\"etacLink\" href=\"#\">",
    " <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
    title=\"Email graphic(s)\"/>",
    " </a>",
    " <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
    " Email",
    " </a>",
    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\">",
    " <div class=\"ttl\">",
    " Genes known to be involved in disorders of sex development (DSD)",
    " </div>",
    " <div class=\"cntnt\">",
    " <table cellspacing=\"0\">",
    " <tbody>",
    " <tr>",
    " <td class=\"subtitle1\">",
    " Gene",
    " </td>",
    " <td class=\"subtitle1\">",
    " Protein",
    " </td>",
    " <td class=\"subtitle1\">",
    " OMIM No.",
    " </td>",
    " <td class=\"subtitle1\">",
    " Locus",
    " </td>",
    " <td class=\"subtitle1\">",
    " Inheritance",
    " </td>",
    " <td class=\"subtitle1\">",
    " Gonad",
    " </td>",
    " <td class=\"subtitle1\">",
    " Mullerian structures",
    " </td>",
    " <td class=\"subtitle1\">",
    " External genitalia",
    " </td>",
    " <td class=\"subtitle1\">",
    " Associated features/variant phenotypes",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"subtitle2_left\" colspan=\"9\">",
    " 46,XY DSD",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"subtitle3_left\" colspan=\"9\">",
    " Disorders of gonadal (testicular) development: single-gene disorders",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent2\">",
    " WT1",
    " </td>",
    " <td>",
    " TF",
    " </td>",
    " <td>",
    " 607102",
    " </td>",
    " <td>",
    " 11p13",
    " </td>",
    " <td>",
    " AD",
    " </td>",
    " <td>",
    " Dysgenetic testis",
    " </td>",
    " <td>",
    " +/-",
    " </td>",
    " <td>",
    " Female or ambiguous",
    " </td>",
    " <td>",
    " Wilms' tumor, renal abnormalities, gonadal tumors (WAGR, Denys-Drash and
    Frasier syndromes)",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent2\">",
    " NR5A1 (SF1)",
    " </td>",
    " <td>",
    " Nuclear receptor TF",
    " </td>",
    " <td>",
    " 184757",
    " </td>",
    " <td>",
    " 9q33",
    " </td>",
    " <td>",
    " AD/AR",
    " </td>",
    " <td>",
    " Dysgenetic testis",
    " </td>",
    " <td>",
    " +/-",
    " </td>",
    " <td>",
    " Female or ambiguous",
    " </td>",
    " <td>",
    " More severe phenotypes include primary adrenal failure; milder phenotypes
    have isolated partial gonadal dysgenesis",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent2\">",
    " SRY",
    " </td>",
    " <td>",
    " TF",
    " </td>",
    " <td>",
    " 480000",
    " </td>",
    " <td>",
    " Yp11.3",
    " </td>",
    " <td>",
    " Y",
    " </td>",
    " <td>",
    " Dysgenetic testis or ovotestis",
    " </td>",
    " <td>",
    " +/-",
    " </td>",
    " <td>",
    " Female or ambiguous",
    " </td>",
    " <td>",
    " &nbsp;",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent2\">",
    " SOX9",
    " </td>",
    " <td>",
    " TF",
    " </td>",
    " <td>",
    " 608160",
    " </td>",
    " <td>",
    " 17q24-25",
    " </td>",
    " <td>",
    " AD",
    " </td>",
    " <td>",
    " Dysgenetic testis or ovotestis",
    " </td>",
    " <td>",
    " +/-",
    " </td>",
    " <td>",
    " Female or ambiguous",
    " </td>",
    " <td>",
    " Camptomelic dysplasia (17q24 rearrangements; milder phenotype than point
    mutations)",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent2\">",
    " DHH",
    " </td>",
    " <td>",
    " Signaling molecule",
    " </td>",
    " <td>",
    " 605423",
    " </td>",
    " <td>",
    " 12q13.1",
    " </td>",
    " <td>",
    " AR",
    " </td>",
    " <td>",
    " Dysgenetic testis",
    " </td>",
    " <td>",
    " +",
    " </td>",
    " <td>",
    " Female",
    " </td>",
    " <td>",
    " The severe phenotype of 1 patient included minifascicular neuropathy;
    other patients have isolated gonadal dysgenesis",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent2\">",
    " ATRX",
    " </td>",
    " <td>",
    " Helicase (? chromatin remodeling)",
    " </td>",
    " <td>",
    " 300032",
    " </td>",
    " <td>",
    " Xq13.3",
    " </td>",
    " <td>",
    " X",
    " </td>",
    " <td>",
    " Dysgenetic testis",
    " </td>",
    " <td>",
    " -",
    " </td>",
    " <td>",
    " Female, ambiguous, or male",
    " </td>",
    " <td>",
    " &alpha;-Thalassemia, mental retardation",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent2\">",
    " ARX",
    " </td>",
    " <td>",
    " TF",
    " </td>",
    " <td>",
    " 300382",
    " </td>",
    " <td>",
    " Xp22.13",
    " </td>",
    " <td>",
    " X",
    " </td>",
    " <td>",
    " Dysgenetic testis",
    " </td>",
    " <td>",
    " -",
    " </td>",
    " <td>",
    " Ambiguous",
    " </td>",
    " <td>",
    " X-linked lissencephaly, epilepsy, temperature instability",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"subtitle3_left\" colspan=\"9\">",
    " Disorders of gonadal (testicular) development: chromosomal changes
    involving key candidate genes",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent2\">",
    " DMRT1",
    " </td>",
    " <td>",
    " TF",
    " </td>",
    " <td>",
    " 602424",
    " </td>",
    " <td>",
    " 9p24.3",
    " </td>",
    " <td>",
    " Monosomic deletion",
    " </td>",
    " <td>",
    " Dysgenetic testis",
    " </td>",
    " <td>",
    " +/-",
    " </td>",
    " <td>",
    " Female or ambiguous",
    " </td>",
    " <td>",
    " Mental retardation",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent2\">",
    " NR0B1 (DAX1)",
    " </td>",
    " <td>",
    " Nuclear receptor TF",
    " </td>",
    " <td>",
    " 300018",
    " </td>",
    " <td>",
    " Xp21.3",
    " </td>",
    " <td>",
    " dupXp21",
    " </td>",
    " <td>",
    " Dysgenetic testis or ovary",
    " </td>",
    " <td>",
    " +/-",
    " </td>",
    " <td>",
    " Female or ambiguous",
    " </td>",
    " <td>",
    " &nbsp;",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent2\">",
    " WNT4",
    " </td>",
    " <td>",
    " Signaling molecule",
    " </td>",
    " <td>",
    " 603490",
    " </td>",
    " <td>",
    " 1p35",
    " </td>",
    " <td>",
    " dup1p35",
    " </td>",
    " <td>",
    " Dysgenetic testis",
    " </td>",
    " <td>",
    " +",
    " </td>",
    " <td>",
    " Ambiguous",
    " </td>",
    " <td>",
    " Mental retardation",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent2\">",
    " WWOX&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;",
    " </td>",
    " <td>",
    " Steroid metabolism&nbsp;",
    " </td>",
    " <td>",
    " 605131&nbsp;",
    " </td>",
    " <td>",
    " 16q23&nbsp;",
    " </td>",
    " <td>",
    " del16q23&nbsp;",
    " </td>",
    " <td>",
    " Dysgenetic&nbsp;testis&nbsp;",
    " </td>",
    " <td>",
    " -",
    " </td>",
    " <td>",
    " Ambiguous&nbsp;",
    " </td>",
    " <td>",
    " 46,XX mother of index case had normal female genitalia and late
    menarche.",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"subtitle3_left\" colspan=\"9\">",
    " Disorders in hormone synthesis or action",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent2\">",
    " LHGCR",
    " </td>",
    " <td>",
    " G-protein receptor",
    " </td>",
    " <td>",
    " 152790",
    " </td>",
    " <td>",
    " 2p21",
    " </td>",
    " <td>",
    " AR",
    " </td>",
    " <td>",
    " Testis",
    " </td>",
    " <td>",
    " -",
    " </td>",
    " <td>",
    " Female, ambiguous, or micropenis",
    " </td>",
    " <td>",
    " Leydig cell hypoplasia",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent2\">",
    " DHCR7",
    " </td>",
    " <td>",
    " Enzyme",
    " </td>",
    " <td>",
    " 602858",
    " </td>",
    " <td>",
    " 11q12-13",
    " </td>",
    " <td>",
    " AR",
    " </td>",
    " <td>",
    " Testis",
    " </td>",
    " <td>",
    " -",
    " </td>",
    " <td>",
    " Variable",
    " </td>",
    " <td>",
    " Smith-Lemli-Opitz syndrome: coarse facies, second-third toe syndactyly,
    failure to thrive, developmental delay, cardiac and visceral abnormalities",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent2\">",
    " StAR (steroidogenic acute regulatory protein)",
    " </td>",
    " <td>",
    " Mitochondrial membrane protein",
    " </td>",
    " <td>",
    " 600617",
    " </td>",
    " <td>",
    " 8p11.2",
    " </td>",
    " <td>",
    " AR",
    " </td>",
    " <td>",
    " Testis",
    " </td>",
    " <td>",
    " -",
    " </td>",
    " <td>",
    " Female",
    " </td>",
    " <td>",
    " Congenital lipoid adrenal hyperplasia (primary adrenal failure), pubertal
    failure",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent2\">",
    " CYP11A1",
    " </td>",
    " <td>",
    " Enzyme",
    " </td>",
    " <td>",
    " 118485",
    " </td>",
    " <td>",
    " 15q23-24",
    " </td>",
    " <td>",
    " AR",
    " </td>",
    " <td>",
    " Testis",
    " </td>",
    " <td>",
    " -",
    " </td>",
    " <td>",
    " Female or ambiguous",
    " </td>",
    " <td>",
    " CAH (primary adrenal failure), pubertal failure",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent2\">",
    " HSD3B2",
    " </td>",
    " <td>",
    " Enzyme",
    " </td>",
    " <td>",
    " 201810",
    " </td>",
    " <td>",
    " 1p13.1",
    " </td>",
    " <td>",
    " AR",
    " </td>",
    " <td>",
    " Testis",
    " </td>",
    " <td>",
    " -",
    " </td>",
    " <td>",
    " Ambiguous",
    " </td>",
    " <td>",
    " CAH, primary adrenal failure, partial androgenization caused by
    dehydroepiandrosterone sulfate",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent2\">",
    " CYP17",
    " </td>",
    " <td>",
    " Enzyme",
    " </td>",
    " <td>",
    " 202110",
    " </td>",
    " <td>",
    " 10q24.3",
    " </td>",
    " <td>",
    " AR",
    " </td>",
    " <td>",
    " Testis",
    " </td>",
    " <td>",
    " -",
    " </td>",
    " <td>",
    " Female, ambiguous, or micropenis",
    " </td>",
    " <td>",
    " CAH, hypertension caused by corticosterone and 11-deoxycorticosterone
    (except in isolated 17,20-lyase deficiency)",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent2\">",
    " POR (P450 oxidoreductase)",
    " </td>",
    " <td>",
    " CYP enzyme electron donor",
    " </td>",
    " <td>",
    " 124015",
    " </td>",
    " <td>",
    " 7q11.2",
    " </td>",
    " <td>",
    " AR",
    " </td>",
    " <td>",
    " Testis",
    " </td>",
    " <td>",
    " -",
    " </td>",
    " <td>",
    " Male or ambiguous",
    " </td>",
    " <td>",
    " Mixed features of 21-hydroxylase deficiency, 17 &alpha;-hydroxylase/17,20-
    lyase deficiency, and aromatase deficiency; sometimes associated with Antley Bixler
    craniosynostosis",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent2\">",
    " HSD17B3",
    " </td>",
    " <td>",
    " Enzyme",
    " </td>",
    " <td>",
    " 605573",
    " </td>",
    " <td>",
    " 9q22",
    " </td>",
    " <td>",
    " AR",
    " </td>",
    " <td>",
    " Testis",
    " </td>",
    " <td>",
    " -",
    " </td>",
    " <td>",
    " Female or ambiguous",
    " </td>",
    " <td>",
    " Partial androgenization at puberty, androstenedione/testosterone ratio",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent2\">",
    " SRD5A2",
    " </td>",
    " <td>",
    " Enzyme",
    " </td>",
    " <td>",
    " 607306",
    " </td>",
    " <td>",
    " 2p23",
    " </td>",
    " <td>",
    " AR",
    " </td>",
    " <td>",
    " Testis",
    " </td>",
    " <td>",
    " -",
    " </td>",
    " <td>",
    " Ambiguous or micropenis",
    " </td>",
    " <td>",
    " Partial androgenization at puberty, testosterone/dihydrotestosterone
    ratio",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent2\">",
    " Anti-Mullerian hormone",
    " </td>",
    " <td>",
    " Signaling molecule",
    " </td>",
    " <td>",
    " 600957",
    " </td>",
    " <td>",
    " 19p13.3-13.2",
    " </td>",
    " <td>",
    " AR",
    " </td>",
    " <td>",
    " Testis",
    " </td>",
    " <td>",
    " +",
    " </td>",
    " <td>",
    " Normal male",
    " </td>",
    " <td rowspan=\"2\">",
    " Persistent Mullerian duct syndrome; male external genitalia, bilateral
    cryptorchidism",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent2\">",
    " Anti-Mullerian hormone receptor",
    " </td>",
    " <td>",
    " Serine-threonine kinase transmembrane receptor",
    " </td>",
    " <td>",
    " 600956",
    " </td>",
    " <td>",
    " 12q13",
    " </td>",
    " <td>",
    " AR",
    " </td>",
    " <td>",
    " Testis",
    " </td>",
    " <td>",
    " +",
    " </td>",
    " <td>",
    " Normal male",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent2\">",
    " Androgen receptor",
    " </td>",
    " <td>",
    " Nuclear receptor TF",
    " </td>",
    " <td>",
    " 313700",
    " </td>",
    " <td>",
    " Xq11-12",
    " </td>",
    " <td>",
    " X",
    " </td>",
    " <td>",
    " Testis",
    " </td>",
    " <td>",
    " -",
    " </td>",
    " <td>",
    " Female, ambiguous, micropenis, or normal male",
    " </td>",
    " <td>",
    " Phenotypic spectrum from CAIS (female external genitalia) and PAIS
    (ambiguous) to normal male genitalia/infertility",
    " </td>",
    " </tr>",
    " </tbody>",
    " </table>",
    " </div>",
    " <div class=\"lgnd\">",
    " Chromosomal rearrangements likely to include key genes are included.",
    " <div class=\"footnotes\">",
    " OMIM: Online Mendelian Inheritance in Man; TF: transcription factor; AD:
    autosomal dominant (often do novo mutation); AR: autosomal recessive; Y: Y-
    chromosomal; X: X-chromosomal.",
    " </div>",
    " <div class=\"reference\">",
    " Reproduced with permission from: Lee PA, Houk CP, Ahmed SF, Hughes IA;
    International Consensus Conference on Intersex organized by the Lawson Wilkins
    Pediatric Endocrine Society and the European Society for Pediatric Endocrinology.
    Consensus statement on management of intersex disorders. International Consensus
    Conference on Intersex. Pediatrics 2006; 118:e488. Copyright &copy; 2006 by the
    AAP.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_18_303=[""].join("\n");
    var outline_f0_18_303=null;

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