var title_f0_8_128="Bepotastine: Patient drug information";

var content_f0_8_128=[" <noscript>",

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" The content on the UpToDate website is not intended nor recommended as a
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"for medical advice, diagnosis, or treatment. Always seek the advice of your own
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" &copy;2013 UpToDate, Inc.",
" </div>",
" <div id=\"drugTitle\">",
" Bepotastine: Patient 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\">",
" <p>",
" (For additional information",
" <a class=\"drug drug_general\" href=\"UTD.htm?7/15/7411?source=see_link\">",
" see \"Bepotastine: Drug information\"",
" </a>",
" )",
" </p>",
" <div class=\"list ubnlist drugH1Div drugBrandNames\" id=\"F8119768\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Brand Names: U.S.",
" </span>",
" <ul>",
" <li>",
" Bepreve&reg;",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yya-os drugH1Div\" id=\"F10022465\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" What is this drug used for?",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2691838",
" </span>",
" </span>",
" <span class=\"content\">",
" It is used to treat eye irritation.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt coi-os drugH1Div\" id=\"F10022464\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" What do I need to tell my doctor before I take this drug?",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2701612",
" </span>",
" </span>",
" <span class=\"content\">",
" If you have an allergy to bepotastine or any other part of this drug.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2705171",
" </span>",
" </span>",
" <span class=\"content\">",
" If you are allergic to any drugs, foods, or other substances. Tell your
doctor about the allergy and what signs you had, like rash; hives; itching;
shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or
any other signs.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yye-os drugH1Div\" id=\"F10022469\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" What are some things I need to know or do while I take this drug?",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699677",
" </span>",
" </span>",
" <span class=\"content\">",
" Keep a list of all your drugs (prescription, natural products, vitamins,
OTC) with you. Give this list to your doctor.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2696717",
" </span>",
" </span>",
" <span class=\"content\">",
" Check all drugs you are taking with your doctor. This drug may not mix well
with some other drugs.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2696947",
" </span>",
" </span>",
" <span class=\"content\">",
" Do not use this drug to treat contact lens irritation.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2696951",
" </span>",
" </span>",
" <span class=\"content\">",
" Do not wear contact lenses if your eyes are red.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2697641",
" </span>",
" </span>",
" <span class=\"content\">",
" Tell your doctor if you are pregnant or plan on getting pregnant. You will
need to talk about the benefits and risks of using this drug while you are
pregnant.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2697636",
" </span>",
" </span>",
" <span class=\"content\">",
" Tell your doctor if you are breast-feeding. You will need to talk about any
risks to your baby.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yyf-os drugH1Div\" id=\"F10022470\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" What are some side effects of this drug?",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698119",
" </span>",
" </span>",
" <span class=\"content\">",
" Headache.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698045",
" </span>",
" </span>",
" <span class=\"content\">",
" Eye irritation.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2696432",
" </span>",
" </span>",
" <span class=\"content\">",
" Bad taste in your mouth. This most often goes back to normal.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yyh-os drugH1Div\" id=\"F10022472\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" What are some side effects that I need to call my doctor about right away?",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698721",
" </span>",
" </span>",
" <span class=\"content\">",
" If you think there has been an overdose, call 1-800-222-1222 (the American
Association of Poison Control Centers), your local poison control center
(file://www.aapcc.org), or emergency room (ER) right away.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699066",
" </span>",
" </span>",
" <span class=\"content\">",
" Signs of an allergic reaction, like rash; hives; itching; red, swollen,
blistered, or peeling skin with or without fever; wheezing; tightness in the chest
or throat; trouble breathing or talking; unusual hoarseness; or swelling of the
mouth, face, lips, tongue, or throat.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699086",
" </span>",
" </span>",
" <span class=\"content\">",
" Sudden change in eyesight, eye pain, or irritation.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698603",
" </span>",
" </span>",
" <span class=\"content\">",
" Any rash.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698977",
" </span>",
" </span>",
" <span class=\"content\">",
" Side effect or health problem is not better or you are feeling worse.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yyc-os drugH1Div\" id=\"F10022467\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" How is this drug best taken?",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2694913",
" </span>",
" </span>",
" <span class=\"content\">",
" For the eye only.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2696257",
" </span>",
" </span>",
" <span class=\"content\">",
" Wash your hands before and after use.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2695781",
" </span>",
" </span>",
" <span class=\"content\">",
" Take out contact lenses before using this drug. Lenses may be put back in
10 minutes after this drug is given. Do not put contacts back in if your eyes are
irritated or infected.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2694779",
" </span>",
" </span>",
" <span class=\"content\">",
" Do not touch the container tip to the eye, lid, or other skin.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2696124",
" </span>",
" </span>",
" <span class=\"content\">",
" Tilt your head back and drop drug into the eye.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2694401",
" </span>",
" </span>",
" <span class=\"content\">",
" After use, keep your eyes closed. Put pressure on the inside corner of the
eye. Do this for 1 to 2 minutes. This keeps the drug in your eye.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2695618",
" </span>",
" </span>",
" <span class=\"content\">",
" Space each eye drug by 5 minutes.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yyd-os drugH1Div\" id=\"F10022468\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" What do I do if I miss a dose?",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2696583",
" </span>",
" </span>",
" <span class=\"content\">",
" Use a missed dose as soon as you think about it.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2696496",
" </span>",
" </span>",
" <span class=\"content\">",
" If it is close to the time for your next dose, skip the missed dose and go
back to your normal time.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2696485",
" </span>",
" </span>",
" <span class=\"content\">",
" Do not use 2 doses or extra doses.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yyi-os drugH1Div\" id=\"F10022473\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" How do I store and/or throw out this drug?",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699336",
" </span>",
" </span>",
" <span class=\"content\">",
" Store at room temperature.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yyj-os drugH1Div\" id=\"F10022474\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" General drug facts",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b259:s2699675",
" </span>",
" </span>",
" <span class=\"content\">",
" If your symptoms or health problems do not get better or if they become
worse, call your doctor.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b259:s2699673",
" </span>",
" </span>",
" <span class=\"content\">",
" Do not share your drugs with others and do not take anyone else's drugs.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b259:s2699678",
" </span>",
" </span>",
" <span class=\"content\">",
" Keep all drugs out of the reach of children and pets.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b259:s2699709",
" </span>",
" </span>",
" <span class=\"content\">",
" If you have any questions about this drug, please talk with your doctor,
pharmacist, or other health care provider.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b259:s3302581",
" </span>",
" </span>",
" <span class=\"content\">",
" In Canada, take any unused drugs to the pharmacy. Also, visit
file://www.hc-sc.gc.ca/hl-vs/iyh-vsv/med/disposal-defaire-eng.php#th to learn about
the right way to get rid of unused drugs.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b259:s2699677",
" </span>",
" </span>",
" <span class=\"content\">",
" Keep a list of all your drugs (prescription, natural products, vitamins,
OTC) with you. Give this list to your doctor.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b259:s2699671",
" </span>",
" </span>",
" <span class=\"content\">",
" These are not all of the side effects that may occur. If you have questions
about side effects, call your doctor. Call your doctor for medical advice about
side effects.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b259:s2699683",
" </span>",
" </span>",
" <span class=\"content\">",
" Talk with the doctor before starting any new drug, including prescription
or OTC, natural products, or vitamins.",
" </span>",
" </li>",
" </ul>",
" </div>",
" </div>",
" <div id=\"topicAgreement\">",
" Use of UpToDate is subject to the",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
target=\"_blank\">",
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" <div id=\"topicVersionRevision\">",
" Topic 11110 Version 30.0",
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" &copy; 2013 UpToDate, Inc. All rights reserved.",
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" Support Tag: [0604-118.195.65.248-FDF33D9AD5-S244013.14]",
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"</div>"].join("\n");
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var outline_f0_8_128=[" <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=\"#F8119768\">",
" Brand Names: U.S.",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F10022465\">",
" What is this drug used for?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F10022464\">",
" What do I need to tell my doctor before I take this drug?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F10022469\">",
" What are some things I need to know or do while I take this drug?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F10022470\">",
" What are some side effects of this drug?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F10022472\">",
" What are some side effects that I need to call my doctor about right away?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F10022467\">",
" How is this drug best taken?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F10022468\">",
" What do I do if I miss a dose?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F10022473\">",
" How do I store and/or throw out this drug?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F10022474\">",
" General drug facts",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" RELATED TOPICS",
" </h1>",
" <div id=\"relatedTopics\">",
" <ul>",
" <li class=\"plainItem\">",
" <a class=\"drug drug_general\" href=\"UTD.htm?7/15/7411?
source=related_link\">",
" Bepotastine: Drug information",
" </a>",
" </li>",
" </ul>",
" </div>",
" </div>"].join("\n");
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" </div>",
" <div class=\"lgnd\">",
" Left spermatic cord",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f0_8_129=[""].join("\n");
var outline_f0_8_129=null;
var title_f0_8_130="Dandy Walker malformation";
var content_f0_8_130=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </div>",
" <div id=\"graphicsLinks\">",
" <a href=\"?imageKey=OBGYN
%2F51726&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=OBGYN
%2F51726&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" 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\" style=\"width: 475px\">",
" <div class=\"ttl\">",
" Dandy-Walker malformation at 27 postmenstrual weeks",
" </div>",
" <div class=\"cntnt\" style=\"width: 455px; height: 273px; background-image:
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" </div>",
" <div class=\"lgnd\">",
" (Panels A-D) Panels A through D are serial coronal sections going from
anterior to posterior showing the dilated lateral ventricles, the large cisterna
magna and the small cerebellum with the missing vermis.",
" <br>",
" (Panel E) Axial section showing the large posterior fossa cyst and the
cerebellar hemispheres widely splayed out.",
" <br>",
" (Panel F) Oblique section showing hydrocephaly.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Courtesy of Ana Monteagudo, MD.",
" </div>",
" </br>",
" </br>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f0_8_130=[""].join("\n");
var outline_f0_8_130=null;
var title_f0_8_131="Endometrial sampling procedures";
var content_f0_8_131=[" <noscript>",
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" Endometrial sampling procedures",
" </div>",
" <div id=\"topicContributors\">",
" <div>",
" <a id=\"authors\">",
" </a>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?0/8/131/contributors\">",
" Author",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/8/131/contributors\">",
" Giuseppe Del Priore, MD, MPH",
" </a>",
" <br/>",
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" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?0/8/131/contributors\">",
" Section Editor",
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" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/8/131/contributors\">",
" Barbara Goff, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?0/8/131/contributors\">",
" Deputy Editor",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/8/131/contributors\">",
" Sandy J Falk, MD",
" </a>",
" <br/>",
" </div>",
" </div>",
" <div id=\"disclosures\">",
" <a href=\"UTD.htm?0/8/131/contributor-disclosure\" target=\"_blank\">",
" Disclosures",
" </a>",
" </div>",
" <div id=\"reviewProcess\">",
" <span>",
" All topics are updated as new evidence becomes available and our",
" </span>",
" <a href=\"/home/editorial-policy\" target=\"_blank\">",
" peer review process",
" </a>",
" <span>",
" is complete.",
" </span>",
" </div>",
" <div id=\"literatureReviewDate\">",
" <span class=\"emphasis\">",
" Literature review current through:",
" </span>",
" Oct 2013.",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <span class=\"emphasis\">",
" This topic last updated:",
" </span>",
" Nov 12, 2012.",
" </div>",
" <div id=\"topicText\">",
" <p class=\"headingAnchor\" id=\"H1\">",
" <span class=\"h1\">",
" INTRODUCTION",
" </span>",
" &nbsp;&mdash;&nbsp;Equipment and techniques for office-based endometrial
sampling has generally replaced the need for diagnostic dilation and curettage
performed in the hospital [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/131/abstract/1\">",
" 1",
" </a>",
" ]. These techniques provide a minimally invasive option for diagnosis of
endometrial cancer, hyperplasia, and other endometrial pathology.",
" </p>",
" <p>",
" Techniques for office procedures for endometrial sampling will be reviewed
here. Dilation and curettage and an overview of the diagnostic approach to
endometrial evaluation for neoplasia, including both noninvasive and invasive
methods, are discussed separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?34/41/35480?
source=see_link\">",
" \"Dilation and curettage\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?37/53/38744?
source=see_link\">",
" \"Evaluation of the endometrium for malignant or premalignant disease\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H2\">",
" <span class=\"h1\">",
" OVERVIEW",
" </span>",
" </p>",
" <p class=\"headingAnchor\" id=\"H1478865\">",
" <span class=\"h2\">",
" Office sampling versus dilation and curettage",
" </span>",
" &nbsp;&mdash;&nbsp;Endometrial sampling offers a number of advantages compared
with dilation and curettage:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Operative setting is an outpatient clinic, rather than an operating room.",
" </li>",
" <li>",
" May be performed without anesthesia or with only local anesthesia.",
" </li>",
" <li>",
" Minimal or no cervical dilation is required.",
" </li>",
" <li>",
" The risk of uterine perforation is decreased (office endometrial sampling:
0.1 to 0.2 percent versus dilation and curettage: 0.3 to 2.6 percent). (See",
" <a class=\"local\" href=\"#H10\">",
" 'Side effects and complications'",
" </a>",
" below and",
" <a class=\"medical medical_review\" href=\"UTD.htm?34/41/35480?
source=see_link&amp;anchor=H21#H21\">",
" \"Dilation and curettage\", section on 'Uterine perforation'",
" </a>",
" .)",
" </li>",
" <li>",
" Operating time is brief; actual sampling time is approximately 5 to 15
seconds.",
" </li>",
" <li>",
" Less expensive.",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H1478872\">",
" <span class=\"h2\">",
" Sample adequacy and condition",
" </span>",
" &nbsp;&mdash;&nbsp;Numerous studies have shown that the endometrium is
adequately evaluated with office sampling techniques. A sample can be obtained in
90 percent or more of patients [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/131/abstract/2\">",
" 2",
" </a>",
" ]. It is important to remember, however, that all sampling devices do not
provide visualization of the uterine cavity. Thus, they perform better when
pathology is global rather than focal, eg, a polyp.",
" </p>",
" <p>",
" Endometrial sampling should provide a histologic specimen of adequate volume
for the pathologist to identify endometrial pathology, and the adequacy of the
sample may depend upon the operator's technique. Society of Gynecologic Oncology
guidelines advise against use of devices that yield crushed (jawed devices),
cauterized (hot loops), or very small (jawed devices) samples [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/131/abstract/3\">",
" 3",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H392089\">",
" <span class=\"h1\">",
" INDICATIONS AND CONTRAINDICATIONS",
" </span>",
" </p>",
" <p class=\"headingAnchor\" id=\"H392116\">",
" <span class=\"h2\">",
" Indications",
" </span>",
" &nbsp;&mdash;&nbsp;Indications for endometrial sampling include:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Evaluation for endometrial neoplasia in women with abnormal uterine bleeding
or specific cervical cytology results (",
" <a class=\"graphic graphic_table graphicRef58600 \" href=\"UTD.htm?
18/38/19052\">",
" table 1",
" </a>",
" )",
" </li>",
" <li>",
" Surveillance for endometrial cancer in women who are at high risk or have a
history of endometrial neoplasia",
" </li>",
" </ul>",
" </p>",
" <p>",
" Women who have been undergone uterus-sparing therapy for endometrial cancer
should have regular endometrial sampling. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?18/23/18810?
source=see_link&amp;anchor=H23#H23\">",
" \"Endometrial carcinoma: Pretreatment evaluation, staging and surgical
treatment\", section on 'Fertility preservation'",
" </a>",
" .)",
" </p>",
" <p>",
" Women with Lynch syndrome (hereditary nonpolyposis colon cancer) require
surveillance for endometrial cancer. There are no consistent guidelines for
screening of women with other risk factors. This must be determined on an
individual basis. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?17/51/18233?
source=see_link&amp;anchor=H11#H11\">",
" \"Endometrial and ovarian cancer screening and prevention in women with Lynch
syndrome (hereditary nonpolyposis colorectal cancer)\", section on 'Endometrial
cancer surveillance'",
" </a>",
" .)",
" </p>",
" <p>",
" Some clinicians perform endometrial sampling as part of the evaluation for
infertility, but this is of limited clinical utility. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?39/61/40921?
source=see_link&amp;anchor=H20#H20\">",
" \"Evaluation of female infertility\", section on 'Endometrial biopsy'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H392123\">",
" <span class=\"h2\">",
" Contraindications",
" </span>",
" &nbsp;&mdash;&nbsp;The only absolute contraindication to endometrial sampling
is the presence of a viable and desired pregnancy.",
" </p>",
" <p>",
" A bleeding diathesis is a relative contraindication since bleeding may be
excessive in such patients. In general, endometrial sampling may be performed in
women who are on anticoagulant therapy if coagulation parameters have consistently
been within the standard therapeutic range. Laboratory testing should be performed
within one month prior to the biopsy. If biopsy is required in a patient with an
uncontrolled bleeding diathesis, consultation should be sought from the physician
managing this aspect of the patient&rsquo;s care. These patients may need to have
anticoagulation reversed or have other treatments (eg,",
" <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
" desmopressin",
" </a>",
" ). Patients with an uncontrolled bleeding diathesis should undergo endometrial
sampling in an operating room setting with access to blood products and anesthesia.
(See",
" <a class=\"medical medical_review\" href=\"UTD.htm?42/18/43305?
source=see_link\">",
" \"Management of hemorrhage in gynecologic surgery\"",
" </a>",
" .)",
" </p>",
" <p>",
" In the presence of acute vaginal, cervical, or pelvic infection, the procedure
should be deferred, if possible, until the infection has been treated.",
" </p>",
" <p>",
" In rare instances, in which endometrial sampling needs to be performed in a
woman with cervical cancer, an obstructing cervical lesion may be a relative
contraindication in some patients due to increased risk of bleeding or uterine
perforation.",
" </p>",
" <p>",
" Sampling can be performed with an intrauterine device in place. In our
practice, we have done so without complications. In addition, an ongoing clinical
trial reports doing so as part of the study design [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/131/abstract/4\">",
" 4",
" </a>",
" ]. No studies have evaluated whether performing endometrial sampling with an
intrauterine device in place decreases the diagnostic performance.",
" </p>",
" <p class=\"headingAnchor\" id=\"H391905\">",
" <span class=\"h1\">",
" PREPROCEDURE PREPARATION",
" </span>",
" </p>",
" <p class=\"headingAnchor\" id=\"H391808\">",
" <span class=\"h2\">",
" Anesthesia",
" </span>",
" &nbsp;&mdash;&nbsp;Office sampling procedures can usually be performed without
significant pain. Discomfort can be minimized by reassuring the woman, explaining
each step before doing it, and avoiding use of mechanical cervical dilators",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" a tenaculum, if possible. Most clinicians recommend an oral nonsteroidal
antiinflammatory drug 30 to 60 minutes prior to the procedure to decrease cramping,
and some administer a paracervical block or use an intrauterine instillation of
local anesthetic [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/131/abstract/5,6\">",
" 5,6",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?39/31/40439?
source=see_link\">",
" \"Pudendal and paracervical block\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H391920\">",
" <span class=\"h2\">",
" Cervical preparation and dilation",
" </span>",
" &nbsp;&mdash;&nbsp;Cervical preparation or dilation is not required in many
women, particularly premenopausal parous women. For women in whom it may be
difficult to pass the sampling device without cervical dilation,",
" <a class=\"drug drug_general\" href=\"UTD.htm?0/41/662?source=see_link\">",
" misoprostol",
" </a>",
" (400 &micro;g) may be given the night before the procedure [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/131/abstract/7\">",
" 7",
" </a>",
" ]. The vaginal route of administration appears to be more effective than oral.
Use of misoprostol for cervical preparation is discussed in detail separately.
(See",
" <a class=\"medical medical_review\" href=\"UTD.htm?9/17/9498?
source=see_link&amp;anchor=H20#H20\">",
" \"Overview of hysteroscopy\", section on 'Cervical preparation and
dilation'",
" </a>",
" .)",
" </p>",
" <p>",
" Women with cervical stenosis may require that the procedure be performed under
general or regional anesthesia, with mechanical cervical dilation or with
ultrasound guidance in a surgical suite.",
" </p>",
" <p class=\"headingAnchor\" id=\"H391927\">",
" <span class=\"h2\">",
" Prophylactic antibiotics",
" </span>",
" &nbsp;&mdash;&nbsp;Prophylactic antibiotics are not necessary during
endometrial sampling for the prevention of surgical site infection or bacterial
endocarditis [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/131/abstract/8\">",
" 8",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?38/55/39800?
source=see_link\">",
" \"Overview of preoperative evaluation and preparation for gynecologic
surgery\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?0/36/585?
source=see_link&amp;anchor=H14#H14\">",
" \"Antimicrobial prophylaxis for bacterial endocarditis\", section on
'Genitourinary and gastrointestinal tracts'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H392000\">",
" <span class=\"h1\">",
" GENERAL PROCEDURE",
" </span>",
" &nbsp;&mdash;&nbsp;The basic steps common to all endometrial sampling
procedures are as follows:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Place the patient in the dorsal lithotomy position.",
" </li>",
" <li>",
" Perform a bimanual examination paying particular attention to the size,
shape, and orientation of the uterus.",
" </li>",
" <li>",
" Insert a speculum and visualize the cervix.",
" </li>",
" <li>",
" Cleaning the cervix with antiseptic solution (eg, povidone-iodine) is
performed by some, but not all, clinicians. Sterile preparation in women who are
allergic to iodine is discussed separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?38/55/39800?
source=see_link&amp;anchor=H17329983#H17329983\">",
" \"Overview of preoperative evaluation and preparation for gynecologic
surgery\", section on 'Vaginal preparation'",
" </a>",
" .)",
" </li>",
" <li>",
" In many women, an endometrial sampling device can be inserted without
grasping the cervix with a tenaculum. Use of a tenaculum increases patient
discomfort.",
" <br/>",
" <br/>",
" A tenaculum should be used if the uterus is not close to axial in position.
In such cases, place a tenaculum (with teeth in a horizontal position) on the
anterior cervical lip and pull outward to straighten the cervicouterine angle.
Straightening the uterine axis reduces the risk of uterine perforation. If a
tenaculum is required and a paracervical block has not been given, we may apply a
local anesthetic (eg, 2 percent",
" <a class=\"drug drug_general\" href=\"UTD.htm?6/7/6264?source=see_link\">",
" benzocaine",
" </a>",
" gel or 20 percent benzocaine spray) to the intended site before placing the
tenaculum. Directing the patient to cough while simultaneously applying the
tenaculum may also decrease discomfort.",
" </li>",
" <li>",
" Using steady and moderate pressure, slowly insert the sampling device
through the cervical os and on to the uterine fundus. Stop when resistance is
met.",
" </li>",
" <li>",
" If the device will not pass through the cervix, attach a tenaculum (if not
already in place) and use a series of small (1 to 4 mm) Hegar dilators to gently
dilate the canal.",
" </li>",
" <li>",
" Many devices are marked with centimeters, so the device can be used to
measure the uterine depth. Average uterine length is 6 to 8 cm.",
" </li>",
" <li>",
" Stabilize the sheath with one hand and pull the piston out as far as
possible to create suction.",
" </li>",
" <li>",
" Remove the device when the entire cavity has been sampled. Expel the
specimen into a formalin container. If there appears to be insufficient tissue for
diagnosis, perform a second pass the device. The same device may be used if it has
not been contaminated; it should not have touched the formalin.",
" </li>",
" <li>",
" Remove the tenaculum, if present. Most bleeding can be controlled with
pressure via cotton swabs or a sponge stick. If bleeding persists, use",
" <a class=\"drug drug_general\" href=\"UTD.htm?19/18/19747?
source=see_link\">",
" ferric subsulfate",
" </a>",
" solution (Monsel's solution) or",
" <a class=\"drug drug_general\" href=\"UTD.htm?41/53/42834?
source=see_link\">",
" silver nitrate",
" </a>",
" sticks to cauterize the site.",
" </li>",
" </ul>",
" </p>",
" <p>",
" When using a suction device, do not let the sheath come outside of the
external os or you will lose the negative pressure. If you do, simply expel the
contents of the sheath into the formalin container onto a sterile non-adhesive
bandage (eg, Telfa), taking care not to contaminate the device, and reinsert the
sheath. Multiple passes are frequently needed to assure specimen adequacy.",
" </p>",
" <p class=\"headingAnchor\" id=\"H4\">",
" <span class=\"h1\">",
" ENDOMETRIAL SUCTION DEVICES",
" </span>",
" &nbsp;&mdash;&nbsp;Suction devices for endometrial sampling consist of a
plunger within a sheath. When the sheath is inserted into the uterus, the plunger
is retracted, creating negative pressure that draws tissue into the sampling
device. Most suction sampling devices utilize low pressure. However, some devices
use a canister or syringe at the proximal end to create higher pressure, which
removes a greater quantity of tissue.",
" </p>",
" <p class=\"headingAnchor\" id=\"H392333\">",
" <span class=\"h2\">",
" Low pressure devices",
" </span>",
" &nbsp;&mdash;&nbsp;Low pressure endometrial suction devices (eg, Pipelle,
Endocell) are the most popular method for sampling the endometrial lining. They are
typically constructed of flexible polypropylene with an outer sheath that is
approximately 3 mm in diameter. The device has a 2.4 mm or smaller side port at the
distal end, through which the endometrial sample is obtained (",
" <a class=\"graphic graphic_picture graphicRef69403 \" href=\"UTD.htm?
33/29/34261\">",
" picture 1",
" </a>",
" ). The flexibility of this type of sampler allows the cannula to conform to
the contour of the uterus and minimizes cramping.",
" </p>",
" <p>",
" In a typical procedure, 5 to 15 percent of the endometrial surface area is
sampled [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/131/abstract/9\">",
" 9",
" </a>",
" ]. Failure to obtain tissue occurs in approximately 0 to 8 percent of low
pressure endometrial suction device procedures [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/131/abstract/10-14\">",
" 10-14",
" </a>",
" ].",
" </p>",
" <p>",
" One approach to improving the tissue adequacy rate is by using a technique
that combines a corkscrew twisting motion and uterine curettage. When using this
method, the device is inserted to the fundus and then withdrawn to the lower
uterine segment, alternating between a corkscrew twisting motion and the motion
usually used to curette the endometrium during a dilation and curettage. Data are
limited on the relative efficacy of the combined approach. In a retrospective chart
review with uniform pathology evaluation, use of a corkscrew twisting motion and
uterine curettage yielded adequate tissue in 95 percent of cases, which was higher
than the 77 percent success rate with a corkscrew technique alone [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/131/abstract/15\">",
" 15",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?34/41/35480?
source=see_link&amp;anchor=H16#H16\">",
" \"Dilation and curettage\", section on 'Curettage'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H392389\">",
" <span class=\"h2\">",
" Higher pressure devices",
" </span>",
" &nbsp;&mdash;&nbsp;Higher pressure devices (eg, Vabra aspirator, Karman
cannula) are used less frequently than low pressure devices because they are less
comfortable for the patient. They are also less flexible, and typically require use
of a tenaculum, cervical dilation, and a paracervical block [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/131/abstract/16\">",
" 16",
" </a>",
" ].",
" </p>",
" <p>",
" An advantage of the Vabra and Karman systems is that they yield a large tissue
sample, comparable to dilation and curettage. These devices are particularly useful
in women with moderate bleeding, since, in our experience, they are not only
diagnostic but also therapeutic.",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Vabra - The Vabra aspirator is available as a 4 mm disposable plastic or a 2
or 3 mm stainless steel device (",
" <a class=\"graphic graphic_picture graphicRef69403 \" href=\"UTD.htm?
33/29/34261\">",
" picture 1",
" </a>",
" ) [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/131/abstract/17\">",
" 17",
" </a>",
" ]. Suction is initiated via an external vacuum pump, which can be noisy. The
tissue sample is retrieved from a tissue trap and placed in formalin.",
" </li>",
" <li>",
" Karman - The Karman cannula comes in diameters of 4 to 6 mm and is made of
flexible plastic with two ports at the distal end [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/131/abstract/18\">",
" 18",
" </a>",
" ]. Suction is provided by a reusable syringe connected to the disposable
cannula. An external vacuum pump can also be used.",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H6\">",
" <span class=\"h1\">",
" ENDOMETRIAL BRUSH",
" </span>",
" &nbsp;&mdash;&nbsp;The endometrial brush (eg, Tao Brush) is a disposable
device with a brush at the distal end, similar to the brush commonly used for
endocervical sampling.",
" </p>",
" <p>",
" Several observational studies have compared endometrial sampling results from
the endometrial brush to those of an endometrial suction sampling device [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/131/abstract/19-24\">",
" 19-24",
" </a>",
" ]. In the largest study, 526 pre- and postmenopausal women were evaluated
using both the Tao Brush and the Pipelle [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/131/abstract/24\">",
" 24",
" </a>",
" ]. In the postmenopausal women, endometrial sampling with the brush resulted
in a significantly higher proportion of adequate endometrial samples compared with
the suction device, whether the techniques were performed with (83 versus 50
percent) or without (61 versus 36 percent) the assistance of hysteroscopy. In
premenopausal women, no differences were found between the two techniques in regard
to adequacy of sampling.",
" </p>",
" <p>",
" Another approach is to use the brush and suction device sequentially during
the same procedure. In one study of 101 women, combined use had a sensitivity and
specificity of 100 percent for diagnosis of endometrial hyperplasia or cancer [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/131/abstract/19\">",
" 19",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H10\">",
" <span class=\"h1\">",
" SIDE EFFECTS AND COMPLICATIONS",
" </span>",
" &nbsp;&mdash;&nbsp;The most common side effect of endometrial sampling is
cramping, which subsides rapidly after the procedure is completed. Cramping tends
to be more severe with the higher pressure suction devices than low pressure
devices, because the former is more rigid, the suction is greater, and larger
samples are removed. Many women will experience light vaginal bleeding or spotting
for several days following the procedure.",
" </p>",
" <p>",
" Vasovagal reactions are not uncommon during endometrial sampling. Such
reactions can generally be prevented by allowing the patient to eat and drink
before the procedure and by minimizing pain through use of analgesics and, if
necessary, local anesthesia. The risk of uterine perforation is approximately 1 to
2 per 1000 procedures [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/131/abstract/15,19,25\">",
" 15,19,25",
" </a>",
" ].",
" </p>",
" <p>",
" Rare complications include excessive uterine bleeding (especially with
undiagnosed coagulopathies), uterine perforation (risk 0.1 to 1.3 percent), pelvic
infection, and bacteremia (including sepsis and endocarditis). Uterine perforation
is discussed in detail separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?4/19/4408?
source=see_link\">",
" \"Uterine perforation during gynecologic procedures\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H11\">",
" <span class=\"h1\">",
" POSTPROCEDURE CARE",
" </span>",
" &nbsp;&mdash;&nbsp;The women should remain in a semirecumbent position for
several minutes after the procedure to reduce the chance of a vasovagal episode.
She may then leave the office if she is not light-headed and there is no heavy
bleeding. Cramping can be managed with nonsteroidal anti-inflammatory drugs,
although persistent cramping is unusual.",
" </p>",
" <p>",
" The patient should call to report any fever, cramping continuing for 48 hours
or more, increasing pain, foul-smelling vaginal discharge, or bleeding heavier than
a normal period. She may resume her usual activities, including coitus, as soon as
she is ready.",
" </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",
" ^{",
" th",
"}",
" to 6",
" ^{",
" th",
"}",
" 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",
" ^{",
" th",
"}",
" to 12",
" ^{",
" th",
"}",
" 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>",
" Beyond the Basics topics (see",
" <a class=\"medical medical_basics\" href=\"UTD.htm?14/25/14738?
source=see_link\">",
" \"Patient information: Heavy periods (The Basics)\"",
" </a>",
" and",
" <a class=\"medical medical_patient\" href=\"UTD.htm?22/18/22820?
source=see_link\">",
" \"Patient information: Abnormal uterine bleeding (Beyond the Basics)\"",
" </a>",
" and",
" <a class=\"medical medical_patient\" href=\"UTD.htm?22/35/23094?
source=see_link\">",
" \"Patient information: Menorrhagia (excessive menstrual bleeding) (Beyond
the Basics)\"",
" </a>",
" ) We encourage you to print or e-mail this topic, or to refer patients to
our public web site",
" <a class=\"external\" href=\"file://www.uptodate.com/patients\">",
" www.uptodate.com/patients",
" </a>",
" , which includes this and other topics.",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H14\">",
" <span class=\"h1\">",
" SUMMARY AND RECOMMENDATIONS",
" </span>",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Office endometrial sampling procedures have largely replaced dilation and
curettage for diagnosis of endometrial neoplasia. The indications for endometrial
sampling include abnormal uterine bleeding or surveillance for endometrial cancer
in women who are at high risk or have a history of endometrial neoplasia. (See",
" <a class=\"local\" href=\"#H392116\">",
" 'Indications'",
" </a>",
" above.)",
" </li>",
" <li>",
" The major contraindication to endometrial sampling is pregnancy, whereas
acute cervical or uterine infection and bleeding diathesis are relative
contraindications. (See",
" <a class=\"local\" href=\"#H392123\">",
" 'Contraindications'",
" </a>",
" above.)",
" </li>",
" <li>",
" An endometrial sample can be obtained in 90 percent or more of patients. All
endometrial sampling devices may perform better when pathology is global rather
than focal. (See",
" <a class=\"local\" href=\"#H1478872\">",
" 'Sample adequacy and condition'",
" </a>",
" above.)",
" </li>",
" <li>",
" Endometrial sampling using a disposable low pressure suction device is a
popular technique because discomfort is minimal. Higher pressure devices are useful
when a larger sample is desired. (See",
" <a class=\"local\" href=\"#H4\">",
" 'Endometrial suction devices'",
" </a>",
" above.)",
" </li>",
" <li>",
" For postmenopausal women, observational data suggest that endometrial
sampling with a brush is more likely to yield an adequate sample than sampling with
low pressure suction device. Combined use of these two devices increased the
diagnostic performance. (See",
" <a class=\"local\" href=\"#H392333\">",
" 'Low pressure devices'",
" </a>",
" above and",
" <a class=\"local\" href=\"#H6\">",
" 'Endometrial brush'",
" </a>",
" above.)",
" </li>",
" <li>",
" The most common procedural side effects are cramping and vasovagal
reactions; uterine perforation is the most serious potential complication. (See",
" <a class=\"local\" href=\"#H10\">",
" 'Side effects and complications'",
" </a>",
" above.)",
" </li>",
" </ul>",
" </p>",
" </div>",
" <div id=\"topicAgreement\">",
" Use of UpToDate is subject to the",
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target=\"_blank\">",
" Subscription and License Agreement",
" </a>",
" .",
" </div>",
" <div class=\"headingAnchor\" id=\"references\">",
" <h1>",
" REFERENCES",
" </h1>",
" <ol id=\"reference\">",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/131/abstract/1\">",
" Grimes DA. Diagnostic dilation and curettage: a reappraisal. Am J Obstet
Gynecol 1982; 142:1.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/131/abstract/2\">",
" Dijkhuizen FP, Mol BW, Br&ouml;lmann HA, Heintz AP. The accuracy of
endometrial sampling in the diagnosis of patients with endometrial carcinoma and
hyperplasia: a meta-analysis. Cancer 2000; 89:1765.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/131/abstract/3\">",
" Trimble CL, Method M, Leitao M, et al. Management of endometrial precancers.
Obstet Gynecol 2012; 120:1160.",
" </a>",
" </li>",
" <li>",
" file://clinicaltrials.gov/show/NCT00788671.",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/131/abstract/5\">",
" Dogan E, Celiloglu M, Sarihan E, Demir A. Anesthetic effect of intrauterine
lidocaine plus naproxen sodium in endometrial biopsy. Obstet Gynecol 2004;
103:347.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/131/abstract/6\">",
" Trolice MP, Fishburne C Jr, McGrady S. Anesthetic efficacy of intrauterine
lidocaine for endometrial biopsy: a randomized double-masked trial. Obstet Gynecol
2000; 95:345.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/131/abstract/7\">",
" G&uuml;ney M, Oral B, Mungan T. Intrauterine lidocaine plus buccal
misoprostol in the endometrial biopsy. Int J Gynaecol Obstet 2007; 97:125.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/131/abstract/8\">",
" ACOG Committee on Practice Bulletins. ACOG Practice Bulletin No. 74.
Antibiotic prophylaxis for gynecologic procedures. Obstet Gynecol 2006; 108:225.",
" </a>",
" </li>",
" <li>",
" APGO educational series on women's health issues. Clinical management of
abnormal uterine bleeding. Association of Professors of Gynecology and Obstetrics,
2006.",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/131/abstract/10\">",
" Gordon SJ, Westgate J. The incidence and management of failed Pipelle
sampling in a general outpatient clinic. Aust N Z J Obstet Gynaecol 1999; 39:115.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/131/abstract/11\">",
" Wagaarachchi PT, Sirisena J. Efficiency of Pipelle device in sampling
endometrium. Acta Obstet Gynecol Scand 2000; 79:793.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/131/abstract/12\">",
" Elsandabesee D, Greenwood P. The performance of Pipelle endometrial sampling
in a dedicated postmenopausal bleeding clinic. J Obstet Gynaecol 2005; 25:32.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/131/abstract/13\">",
" Polena V, Mergui JL, Zerat L, Sananes S. The role of Pipelle Mark II
sampling in endometrial disease diagnosis. Eur J Obstet Gynecol Reprod Biol 2007;
134:233.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/131/abstract/14\">",
" Moberger B, Nilsson S, Palmstierna S, et al. A multicenter study comparing
two endometrial sampling devices--Medscand Endorette and Pipelle de Cornier. Acta
Obstet Gynecol Scand 1998; 77:764.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/131/abstract/15\">",
" Sierecki AR, Gudipudi DK, Montemarano N, Del Priore G. Comparison of
endometrial aspiration biopsy techniques: specimen adequacy. J Reprod Med 2008;
53:760.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/131/abstract/16\">",
" Kaunitz AM, Masciello A, Ostrowski M, Rovira EZ. Comparison of endometrial
biopsy with the endometrial Pipelle and Vabra aspirator. J Reprod Med 1988;
33:427.",
" </a>",
" </li>",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/131/abstract/17\">",
" Einerth Y. Vacuum curettage by the Vabrar method. A simple procedure for
endometrial diagnosis. Acta Obstet Gynecol Scand 1982; 61:373.",
" </a>",
" </li>",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/131/abstract/18\">",
" Suarez RA, Grimes DA, Majmudar B, Benigno BB. Diagnostic endometrial
aspiration with the Karman cannula. J Reprod Med 1983; 28:41.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/131/abstract/19\">",
" Del Priore G, Williams R, Harbatkin CB, et al. Endometrial brush biopsy for
the diagnosis of endometrial cancer. J Reprod Med 2001; 46:439.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/131/abstract/20\">",
" Critchley HO, Warner P, Lee AJ, et al. Evaluation of abnormal uterine
bleeding: comparison of three outpatient procedures within cohorts defined by age
and menopausal status. Health Technol Assess 2004; 8:iii.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/131/abstract/21\">",
" Yang GC, Wan LS, Del Priore G. Factors influencing the detection of uterine
cancer by suction curettage and endometrial brushing. J Reprod Med 2002; 47:1005.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/131/abstract/22\">",
" Yang GC, Wan LS. Endometrial biopsy using the Tao Brush method. A study of
50 women in a general gynecologic practice. J Reprod Med 2000; 45:109.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/131/abstract/23\">",
" Maksem JA. Performance characteristics of the Indiana University Medical
Center endometrial sampler (Tao Brush) in an outpatient office setting, first
year's outcomes: recognizing histological patterns in cytology preparations of
endometrial brushings. Diagn Cytopathol 2000; 22:186.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/131/abstract/24\">",
" Williams AR, Brechin S, Porter AJ, et al. Factors affecting adequacy of
Pipelle and Tao Brush endometrial sampling. BJOG 2008; 115:1028.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/131/abstract/25\">",
" Cooper JM, Erickson ML. Endometrial sampling techniques in the diagnosis of
abnormal uterine bleeding. Obstet Gynecol Clin North Am 2000; 27:235.",
" </a>",
" </li>",
" </ol>",
" </div>",
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" <div id=\"innerOutline\">",
" <h1>",
" TOPIC OUTLINE",
" </h1>",
" <div id=\"outline\">",
" <ul>",
" <li>",
" <a class=\"sr_button\" href=\"#H14\" id=\"summRecButton\">",
" <span>",
" SUMMARY &amp; RECOMMENDATIONS",
" </span>",
" </a>",
" </li>",
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" INTRODUCTION",
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" OVERVIEW",
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" Office sampling versus dilation and curettage",
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" Sample adequacy and condition",
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" INDICATIONS AND CONTRAINDICATIONS",
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" <a class=\"outlineLink\" href=\"#H392116\">",
" Indications",
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" Contraindications",
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" PREPROCEDURE PREPARATION",
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" <a class=\"outlineLink\" href=\"#H391808\">",
" Anesthesia",
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" <a class=\"outlineLink\" href=\"#H391920\">",
" Cervical preparation and dilation",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H391927\">",
" Prophylactic antibiotics",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H392000\">",
" GENERAL PROCEDURE",
" </a>",
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" ENDOMETRIAL SUCTION DEVICES",
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" Low pressure devices",
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" Higher pressure devices",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H6\">",
" ENDOMETRIAL BRUSH",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H10\">",
" SIDE EFFECTS AND COMPLICATIONS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H11\">",
" POSTPROCEDURE CARE",
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" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#PATIENT_INFORMATION\">",
" INFORMATION FOR PATIENTS",
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" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H14\">",
" SUMMARY AND RECOMMENDATIONS",
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" <a href=\"#references\">",
" REFERENCES",
" </a>",
" </li>",
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" <h1>",
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title=\"picture 1\">",
" Pipelle and Vabra instruments",
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1\">",
" Indications endometrial evaluat",
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" </div>",
" <h1>",
" RELATED TOPICS",
" </h1>",
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" </a>",
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" </div>",
" </div>"].join("\n");
var title_f0_8_132="Measurement of cortisol in serum and saliva";
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" Measurement of cortisol in serum and saliva",
" </div>",
" <div id=\"topicContributors\">",
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" Author",
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" <div id=\"topicText\">",
" <p class=\"headingAnchor\" id=\"H1\">",
" <span class=\"h1\">",
" INTRODUCTION",
" </span>",
" &nbsp;&mdash;&nbsp;Measurements of cortisol in serum (or occasionally plasma)
are extremely useful in the diagnosis of hypercortisolism and adrenal
insufficiency. It is important to appreciate the many factors that can affect the
serum cortisol concentration and in particular the episodic secretion of cortisol
and the resulting diurnal variation in serum cortisol, which makes the
interpretation of a single value hazardous. Measurements of the salivary cortisol
may offer some advantages over measurements of serum cortisol. Methods of
interpretation of cortisol assays will be reviewed here. Their use in the diagnosis
of adrenal disorders is reviewed separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?21/25/21913?
source=see_link\">",
" \"Establishing the diagnosis of Cushing's syndrome\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?43/46/44777?
source=see_link\">",
" \"Diagnosis of adrenal insufficiency in adults\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H2\">",
" <span class=\"h1\">",
" MEASUREMENT OF SERUM CORTISOL",
" </span>",
" &nbsp;&mdash;&nbsp;Cortisol has been measured in serum by several methods.
Although many of them are no longer in routine use, the important assays are
mentioned to permit one to interpret the older literature.",
" </p>",
" <p class=\"headingAnchor\" id=\"H3\">",
" <span class=\"h2\">",
" Methods of measurement",
" </span>",
" </p>",
" <p class=\"headingAnchor\" id=\"H4\">",
" <span class=\"h3\">",
" Porter-Silber chromogens",
" </span>",
" &nbsp;&mdash;&nbsp;Serum cortisol was first measured by assay of Porter-Silber
chromogens (17,21-dihydroxy-20-ketosteroids, referred to as 17-
hydroxycorticosteroids, or 17-OHCS) [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/1\">",
" 1",
" </a>",
" ]. This method is no longer used.",
" </p>",
" <p class=\"headingAnchor\" id=\"H5\">",
" <span class=\"h3\">",
" Competitive protein-binding assay",
" </span>",
" &nbsp;&mdash;&nbsp;This assay uses competition for binding sites on cortisol-
binding globulin (CBG, or transcortin) to quantify cortisol [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/2,3\">",
" 2,3",
" </a>",
" ]. Its advantage is lack of drug interference; its disadvantage is that",
" <a class=\"drug drug_general\" href=\"UTD.htm?32/48/33536?source=see_link\">",
" prednisolone",
" </a>",
" and several endogenous steroids, some of which may be increased in pregnancy,
adrenal carcinoma, congenital adrenal hyperplasia, and after administration of
adrenal enzyme inhibitors, bind to CBG and falsely elevate serum cortisol values.
Interfering steroids can be removed before assay by solvent partition or thin layer
chromatography (TLC).",
" </p>",
" <p class=\"headingAnchor\" id=\"H6\">",
" <span class=\"h3\">",
" Fluorometric assay",
" </span>",
" &nbsp;&mdash;&nbsp;This assay exploits the fluorescence of 4-11-beta, 21-
dihydroxy-3,20-ketosteroids (11-hydroxycorticosteroids, or 11-OHCS) in sulfuric
acid and alcohol [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/4\">",
" 4",
" </a>",
" ]. Cortisol and corticosterone are detected by this assay; potent synthetic
glucocorticoids are not. Its advantages are simplicity and relative specificity;
its disadvantage is that",
" <a class=\"drug drug_general\" href=\"UTD.htm?17/22/17767?source=see_link\">",
" spironolactone",
" </a>",
" ,",
" <a class=\"drug drug_general\" href=\"UTD.htm?14/46/15080?source=see_link\">",
" quinine",
" </a>",
" ,",
" <a class=\"drug drug_general\" href=\"UTD.htm?0/48/777?source=see_link\">",
" quinidine",
" </a>",
" , niacin, and benzoyl alcohol also fluoresce in those solvents and therefore
falsely elevate cortisol values.",
" </p>",
" <p class=\"headingAnchor\" id=\"H7\">",
" <span class=\"h3\">",
" Radioreceptor assay",
" </span>",
" &nbsp;&mdash;&nbsp;This assay uses the type II glucocorticoid cytosol receptor
as a cortisol-binding agent [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/5\">",
" 5",
" </a>",
" ]. Its advantage is its specificity for bioactive steroids, including
synthetic glucocorticoids; its disadvantage is the limited supply and instability
of the receptor. As a result, this assay is not widely available.",
" </p>",
" <p class=\"headingAnchor\" id=\"H8\">",
" <span class=\"h3\">",
" Radioimmunoassay",
" </span>",
" &nbsp;&mdash;&nbsp;Radioimmunoassays for cortisol use polyclonal or monoclonal
antibodies that are raised to a cortisol analogue that has been conjugated to a
protein carrier. Each antibody is characterized in terms of its affinity and
crossreactivity with other endogenous or exogenous steroids found in serum.
Antibody, labeled cortisol tracer, and cortisol standard are used to perform the
assay. The results are dependent upon the specificity of the antibody used in the
assay. Both liquid-phase and solid-phase assays of requisite sensitivity and
specificity are widely available in reference laboratories and in kit form. Serum
total cortisol is measured.",
" </p>",
" <p class=\"headingAnchor\" id=\"H9\">",
" <span class=\"h3\">",
" Other immunoassays",
" </span>",
" &nbsp;&mdash;&nbsp;Variations on radioimmunoassays using fluorescent,
chemiluminescent, and other labels in place of radioisotopic labels, and two-site
antibody designs (one antibody is bound to a solid substrate, the other carries the
radioactive or other label, and the steroid forms a bridge between them) have
similar sensitivity and specificity and are available for use in automated
analyzers. The results, like those of radioimmunoassay, are dependent upon the
specificity of the antibody used in the assay.",
" </p>",
" <p class=\"headingAnchor\" id=\"H10\">",
" <span class=\"h3\">",
" Structurally-based assays",
" </span>",
" &nbsp;&mdash;&nbsp;In contrast to antibody-based assays, structurally-based
assays (HPLC, mass spectrometry) are highly specific for the cortisol molecule;
they also can measure synthetic steroids [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/6\">",
" 6",
" </a>",
" ]. The development of high-throughput techniques to simultaneously measure
multiple samples makes these labor-intense assays feasible for commercial use [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/7\">",
" 7",
" </a>",
" ]. This method separates cortisol from other steroids and steroid metabolites;
cortisol is then measured fluorometrically or spectrophotometrically [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/8\">",
" 8",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H11\">",
" <span class=\"h2\">",
" Normal values",
" </span>",
" &nbsp;&mdash;&nbsp;The serum cortisol concentration normally reflects that of
corticotropin (ACTH) and therefore has circadian rhythmicity (",
" <a class=\"graphic graphic_figure graphicRef57231 \" href=\"UTD.htm?
6/17/6431\">",
" figure 1",
" </a>",
" and",
" <a class=\"graphic graphic_figure graphicRef61069 \" href=\"UTD.htm?
36/46/37614\">",
" figure 2",
" </a>",
" ). Normal values vary with the particular assay. The following values are
representative of an average radioimmunoassay; those obtained by competitive
protein binding assay would be similar, and fluorometric assay results are about
3",
" <span class=\"nowrap\">",
" mcg/dL",
" </span>",
" (85",
" <span class=\"nowrap\">",
" nmol/L)",
" </span>",
" higher [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/9\">",
" 9",
" </a>",
" ].",
" </p>",
" <p>",
" In normal subjects serum cortisol concentrations are higher in the early
morning (about 6 AM), ranging from 10 to 20",
" <span class=\"nowrap\">",
" mcg/dL",
" </span>",
" (275 to 555",
" <span class=\"nowrap\">",
" nmol/L).",
" </span>",
" Serum cortisol concentrations range from 3 to 10",
" <span class=\"nowrap\">",
" mcg/dL",
" </span>",
" (85 to 275",
" <span class=\"nowrap\">",
" nmol/L)",
" </span>",
" at 4 PM, and the concentrations are lowest, less than 5",
" <span class=\"nowrap\">",
" mcg/dL",
" </span>",
" (140",
" <span class=\"nowrap\">",
" nmol/L),",
" </span>",
" one hour after the usual time of sleep (",
" <a class=\"graphic graphic_figure graphicRef61069 \" href=\"UTD.htm?
36/46/37614\">",
" figure 2",
" </a>",
" ).",
" </p>",
" <p class=\"headingAnchor\" id=\"H12\">",
" <span class=\"h2\">",
" Interpretation",
" </span>",
" &nbsp;&mdash;&nbsp;Cortisol secretion is episodic and the normal ranges are
broad. A single serum value, if it falls within the normal range, is inconclusive.
An individual can have partial pituitary or adrenal insufficiency but maintain
plasma ACTH and serum cortisol concentrations within their respective normal
ranges. For these reasons, stimulation or suppression testing should be performed
when there is doubt. Nevertheless, samples drawn at the appropriate time for the
suspected endocrine dysfunction can be very helpful in excluding adrenal
hypofunction or hyperfunction.",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Patients with primary or secondary adrenal insufficiency have low early
morning serum cortisol concentrations. If the value is greater than 10",
" <span class=\"nowrap\">",
" mcg/dL",
" </span>",
" (276",
" <span class=\"nowrap\">",
" nmol/L),",
" </span>",
" it is unlikely that the patient has clinically important adrenal
insufficiency, whereas if it is less than 3",
" <span class=\"nowrap\">",
" mcg/dL",
" </span>",
" (83",
" <span class=\"nowrap\">",
" nmol/L),",
" </span>",
" the probability of adrenal insufficiency is high. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?43/46/44777?
source=see_link\">",
" \"Diagnosis of adrenal insufficiency in adults\"",
" </a>",
" .) Since serum cortisol is often undetectable one hour after the beginning
of sleep, measurement at this time does not identify patients with adrenal
insufficiency.",
" </li>",
" <li>",
" Patients with congenital adrenal hyperplasia may have normal or low serum
cortisol values (corresponding to simple virilizing and \"late-onset\" CYP21A2
deficiency types) in the early morning.",
" </li>",
" <li>",
" Most patients with Cushing's syndrome have early morning serum cortisol
concentrations within or slightly above the normal range. In contrast, serum
cortisol concentrations one hour after sleep are almost always high (greater than
7.5",
" <span class=\"nowrap\">",
" mcg/dL",
" </span>",
" [207 nmol]) and are often equal to the early morning values (ie, they have
an abnormal or absent circadian rhythm) [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/10\">",
" 10",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?21/25/21913?
source=see_link\">",
" \"Establishing the diagnosis of Cushing's syndrome\"",
" </a>",
" .)",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H13\">",
" <span class=\"h2\">",
" Important caveats",
" </span>",
" &nbsp;&mdash;&nbsp;Cortisol secretion normally reflects ACTH secretion. As a
result, the same caveats concerning circadian rhythmicity, stress, and
glucocorticoid administration also pertain to it, except that recent",
" <a class=\"drug drug_general\" href=\"UTD.htm?31/49/32528?source=see_link\">",
" hydrocortisone",
" </a>",
" (cortisol) or cortisone administration may result in high serum cortisol
concentrations. The longer disappearance half-time of cortisol than of ACTH (about
80 versus eight minutes) and the several minute lag in its secretion after ACTH
stimulation tend to damp excursions in serum cortisol relative to those of ACTH.",
" </p>",
" <p>",
" Several other factors must be considered in interpreting serum cortisol
results.",
" </p>",
" <p class=\"headingAnchor\" id=\"H14\">",
" <span class=\"h3\">",
" CBG",
" </span>",
" &nbsp;&mdash;&nbsp;Serum cortisol concentrations do not correlate well with
cortisol production rates unless the CBG concentration is accounted for [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/11\">",
" 11",
" </a>",
" ]. Hepatic CBG synthesis is increased by estrogens [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/12-14\">",
" 12-14",
" </a>",
" ], and early morning serum total cortisol concentrations of 50",
" <span class=\"nowrap\">",
" mcg/dL",
" </span>",
" (1400",
" <span class=\"nowrap\">",
" nmol/L)",
" </span>",
" or higher are not unusual during pregnancy or high dose oral contraceptive use
[",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/15,16\">",
" 15,16",
" </a>",
" ]. Cortisol dissociates rapidly from CBG, so that early morning values are
usually normal in these women. Insulin and insulin-like growth factor-1 inhibit CBG
secretion in vitro, and serum CBG concentrations inversely correlated with indexes
of insulin secretion such as fasting serum glucose concentrations and A1C are
values [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/17\">",
" 17",
" </a>",
" ]. Serum CBG concentration is increased in obese patients who have glucose
intolerance. Some individuals have low levels of CBG on a genetic basis.",
" </p>",
" <p class=\"headingAnchor\" id=\"H15\">",
" <span class=\"h3\">",
" Hepatic and renal dysfunction",
" </span>",
" &nbsp;&mdash;&nbsp;Even relatively severe hepatic dysfunction has little
effect on serum cortisol concentrations [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/18\">",
" 18",
" </a>",
" ]. Renal failure also has little effect on them, although retained cortisol
metabolites may interfere in some radioimmunoassays [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/19\">",
" 19",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H16\">",
" <span class=\"h3\">",
" Thyroid hormone",
" </span>",
" &nbsp;&mdash;&nbsp;Thyroid hormone regulates the rate of cortisol metabolism,
but hypothalamic-pituitary feedback mechanisms are intact and serum cortisol
concentrations are within normal limits in patients with hypothyroidism or
hyperthyroidism.",
" </p>",
" <p class=\"headingAnchor\" id=\"H17\">",
" <span class=\"h3\">",
" Body weight",
" </span>",
" &nbsp;&mdash;&nbsp;Body weight has no appreciable effect on serum cortisol
concentrations, but severe malnutrition apparently has a greater inhibitory effect
on cortisol metabolism than on cortisol production, increasing serum cortisol
concentrations slightly [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/20\">",
" 20",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H18\">",
" <span class=\"h3\">",
" Age",
" </span>",
" &nbsp;&mdash;&nbsp;It requires one year or more for infants to establish an
adult sleep-wake cycle, entrain their circadian rhythms, and establish an adult
pattern of ACTH and cortisol secretion [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/21\">",
" 21",
" </a>",
" ]. Except for these changes in infants and the fact that, for the first
several days of life, normal infants produce more cortisone than cortisol and have
low serum cortisol concentrations [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/22\">",
" 22",
" </a>",
" ], age has no effect on serum cortisol concentrations.",
" </p>",
" <p class=\"headingAnchor\" id=\"H19\">",
" <span class=\"h3\">",
" Depression",
" </span>",
" &nbsp;&mdash;&nbsp;Major depressive disorders, especially severe melancholic
depression, can result in cortisol dynamics similar to those of Cushing's disease
[",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/23-25\">",
" 23-25",
" </a>",
" ]. However, most ambulatory patients with major depression have normal hour-
of-sleep serum cortisol concentrations.",
" </p>",
" <p class=\"headingAnchor\" id=\"H20\">",
" <span class=\"h3\">",
" Synthetic glucocorticoids",
" </span>",
" &nbsp;&mdash;&nbsp;Exogenously administered glucocorticoids can alter serum
cortisol values either directly, if they cross-react with an antibody, leading to
spurious elevations, or indirectly, if they suppress the hypothalamic-pituitary-
adrenal axis, leading to low values. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?43/46/44777?
source=see_link\">",
" \"Diagnosis of adrenal insufficiency in adults\"",
" </a>",
" .)",
" </p>",
" <p>",
" Cross-reactivity depends upon the specificity of the antibody for cortisol.
This possibility is evaluated during the development of antibody-based commercial
assays and the results are available in the assay kit instructions, or from the
company.",
" </p>",
" <p>",
" In contrast to antibody-based assays, structurally-based assays (HPLC, mass
spectrometry) are highly specific for the cortisol molecule; they also can measure
synthetic steroids [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/6\">",
" 6",
" </a>",
" ]. The development of high-throughput techniques to simultaneously measure
multiple samples makes these labor-intense assays feasible for commercial use [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/7\">",
" 7",
" </a>",
" ]. Such assays are useful to evaluate surreptitious ingestion of synthetic
steroids or potential cross-reaction in an antibody-based assay.",
" </p>",
" <p>",
" Depending upon the dose and duration of exogenous glucocorticoid
administration, serum cortisol values may also be suppressed, reflecting secondary
adrenal insufficiency. If this is the case, medications should be tapered rather
than stopped for testing. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?21/37/22103?
source=see_link\">",
" \"Glucocorticoid withdrawal\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H21\">",
" <span class=\"h3\">",
" Non-glucocorticoid drugs",
" </span>",
" &nbsp;&mdash;&nbsp;Several drugs induce hepatic cytochrome P-450 enzymes that
metabolize steroids. Barbiturates,",
" <a class=\"drug drug_general\" href=\"UTD.htm?34/48/35594?source=see_link\">",
" phenytoin",
" </a>",
" ,",
" <a class=\"drug drug_general\" href=\"UTD.htm?10/31/10746?source=see_link\">",
" rifampin",
" </a>",
" , aminoglutethimide, and",
" <a class=\"drug drug_general\" href=\"UTD.htm?15/58/16293?source=see_link\">",
" mitotane",
" </a>",
" increase the metabolic clearance of steroids and of",
" <a class=\"drug drug_general\" href=\"UTD.htm?15/12/15556?source=see_link\">",
" metyrapone",
" </a>",
" . They have a preferential effect on synthetic 9-fluoro steroids (eg,",
" <a class=\"drug drug_general\" href=\"UTD.htm?33/4/33856?source=see_link\">",
" dexamethasone",
" </a>",
" and",
" <a class=\"drug drug_general\" href=\"UTD.htm?21/9/21655?source=see_link\">",
" fludrocortisone",
" </a>",
" ) as compared with natural steroids.",
" </p>",
" <p>",
" These drugs do not alter serum cortisol concentrations in normal subjects, but
they can interfere with",
" <a class=\"drug drug_general\" href=\"UTD.htm?33/4/33856?source=see_link\">",
" dexamethasone",
" </a>",
" suppression and",
" <a class=\"drug drug_general\" href=\"UTD.htm?15/12/15556?source=see_link\">",
" metyrapone",
" </a>",
" stimulation tests and necessitate increased steroid replacement dose in
patients with adrenal insufficiency.",
" </p>",
" <p class=\"headingAnchor\" id=\"H22\">",
" <span class=\"h3\">",
" Alcohol abuse",
" </span>",
" &nbsp;&mdash;&nbsp;Alcohol abuse sufficient to increase serum hepatic enzyme
concentrations, especially gamma-glutamyltransferase, can cause pseudo-Cushing's
syndrome and high serum cortisol concentrations [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/26\">",
" 26",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H23\">",
" <span class=\"h3\">",
" Sepsis",
" </span>",
" &nbsp;&mdash;&nbsp;Patients with severe illness and sepsis have reduced CBG
and albumin levels that result in lower serum cortisol levels [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/27,28\">",
" 27,28",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H24\">",
" <span class=\"h1\">",
" SERUM FREE CORTISOL",
" </span>",
" &nbsp;&mdash;&nbsp;The biologically active fraction of cortisol in serum is
free cortisol. Although a variety of methods have been developed for measuring
serum free cortisol [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/5,29-32\">",
" 5,29-32",
" </a>",
" ], they are technically demanding and expensive and are not in general use.
However, recent reports of decreased total cortisol levels in sepsis and critical
illness have led to increased interest in measurement or calculation of free
cortisol levels in these patients [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/27,28,33\">",
" 27,28,33",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?24/20/24905?
source=see_link&amp;anchor=H20#H20\">",
" \"Evaluation of the response to ACTH in adrenal insufficiency\", section on
'Critical illness'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H25\">",
" <span class=\"h1\">",
" CORTISOL PRECURSORS",
" </span>",
" &nbsp;&mdash;&nbsp;Several biosynthetic precursors of cortisol, including
pregnenolone, 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone, and 11-
deoxycortisol, can be measured by radioimmunoassay directly or after solvent
partition",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" chromatography [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/30,34\">",
" 30,34",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H26\">",
" <span class=\"h2\">",
" Normal values",
" </span>",
" &nbsp;&mdash;&nbsp;The normal values for these compounds are as follows:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Serum 11-deoxycortisol is undetectable in normal subjects by current assays
(ie, &lt;1",
" <span class=\"nowrap\">",
" mcg/dL",
" </span>",
" or 30",
" <span class=\"nowrap\">",
" nmol/L",
" </span>",
" at 8 AM).",
" </li>",
" <li>",
" The early morning serum 17-hydroxyprogesterone concentration ranges from 60
to 300",
" <span class=\"nowrap\">",
" ng/dL",
" </span>",
" (1.8 to 19",
" <span class=\"nowrap\">",
" nmol/L60",
" </span>",
" to 300",
" <span class=\"nowrap\">",
" ng/dL)",
" </span>",
" in men, 20 to 100",
" <span class=\"nowrap\">",
" ng/dL",
" </span>",
" (0.6 to 3",
" <span class=\"nowrap\">",
" nmol/L)",
" </span>",
" in women during the follicular phase of the menstrual cycle, 50 to 350",
" <span class=\"nowrap\">",
" ng/dL",
" </span>",
" (1.5 to 10.6",
" <span class=\"nowrap\">",
" nmol/L)",
" </span>",
" during the luteal phase, and 600",
" <span class=\"nowrap\">",
" ng/dL",
" </span>",
" (18",
" <span class=\"nowrap\">",
" nmol/L)",
" </span>",
" and more by the end of pregnancy.",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H27\">",
" <span class=\"h2\">",
" Interpretation",
" </span>",
" &nbsp;&mdash;&nbsp;These assays are not commonly used for assessment of
hypothalamic-pituitary-adrenal function, but some of them do have specific
applications.",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Serum 17-hydroxyprogesterone can be measured before and after administration
of cosyntropin (ACTH) in patients expected to have the 21-hydroxylase (P-450c21)
deficiency variant of congenital adrenal hyperplasia [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/35,36\">",
" 35,36",
" </a>",
" ]. Return of the early morning serum 17-hydroxypregnenolone or 17-
hydroxyprogesterone concentration to normal can be used as an index of the adequacy
of treatment in this disorder [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/37\">",
" 37",
" </a>",
" ].",
" </li>",
" <li>",
" Serum 11-deoxycortisol can be measured in tests of pituitary ACTH secretory
reserve using",
" <a class=\"drug drug_general\" href=\"UTD.htm?15/12/15556?
source=see_link\">",
" metyrapone",
" </a>",
" &nbsp;[",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/38\">",
" 38",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?15/48/16135?
source=see_link\">",
" \"Metyrapone stimulation tests\"",
" </a>",
" .)",
" </li>",
" <li>",
" One or more of these cortisol precursors may be increased in the serum of
patients with adrenal carcinoma [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/39\">",
" 39",
" </a>",
" ].",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H28\">",
" <span class=\"h1\">",
" MEASUREMENT OF SALIVARY CORTISOL CONCENTRATION",
" </span>",
" &nbsp;&mdash;&nbsp;Serum free cortisol diffuses freely into saliva. Therefore,
measurements of salivary cortisol more accurately reflect serum free cortisol
concentrations than do measurements of serum total cortisol. The salivary cortisol
concentration is independent of salivary flow rate [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/40,41\">",
" 40,41",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H29\">",
" <span class=\"h2\">",
" Assay",
" </span>",
" &nbsp;&mdash;&nbsp;Saliva (2.5 mL) is obtained after rinsing the mouth but
before brushing the teeth, either by unstimulated flow or after chewing uncoated
gum or a cotton tube (Plain Salivette, Sarstedt, Newton, NC), and can be stored at
room temperature for many days [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/42\">",
" 42",
" </a>",
" ] or frozen for extended periods. The sample is thawed, centrifuged at 1500 x
g for 10 min at 4&ordm;C, and 2 mL of the supernatant is added to 10 mL of
dichloromethane [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/43\">",
" 43",
" </a>",
" ]. The dichloromethane is aspirated and evaporated, and the dried extract is
reconstituted in assay buffer and assayed by competitive protein-binding assay [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/2,44\">",
" 2,44",
" </a>",
" ], radioimmunoassay [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/44,45\">",
" 44,45",
" </a>",
" ], or enzyme immunoassay [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/46\">",
" 46",
" </a>",
" ]. Radioimmunoassay of unextracted saliva has also been described [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/47,48\">",
" 47,48",
" </a>",
" ].",
" </p>",
" <p>",
" With the development of high-affinity antisera that react specifically with
the D ring of cortisol, sensitivity has been improved, and interference by other
steroids has been minimized.",
" </p>",
" <p class=\"headingAnchor\" id=\"H30\">",
" <span class=\"h2\">",
" Normal values",
" </span>",
" &nbsp;&mdash;&nbsp;Salivary cortisol concentrations vary diurnally, with
concentration of about 5.6",
" <span class=\"nowrap\">",
" ng/mL",
" </span>",
" (15.4",
" <span class=\"nowrap\">",
" nmol/L)",
" </span>",
" at 8 to 9 AM and about 1",
" <span class=\"nowrap\">",
" ng/mL",
" </span>",
" (2.8",
" <span class=\"nowrap\">",
" nmol/L)",
" </span>",
" at 11 PM [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/43,45,48\">",
" 43,45,48",
" </a>",
" ]&nbsp;(",
" <a class=\"graphic graphic_table graphicRef57112 \" href=\"UTD.htm?
37/33/38427\">",
" table 1",
" </a>",
" ). The values in obese men and women are similar [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/43\">",
" 43",
" </a>",
" ]. Additional work is needed to evaluate the late night normal range in older
patients with medical illness [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/49\">",
" 49",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H31\">",
" <span class=\"h2\">",
" Interpretation",
" </span>",
" &nbsp;&mdash;&nbsp;Morning salivary cortisol concentrations are decreased in
adrenal insufficiency, while late evening salivary cortisol concentrations are
increased in Cushing's syndrome. Both the competitive protein-binding assay and
cortisol radioimmunoassays crossreact with other steroids. The competitive protein-
binding assay crossreacts with 17-hydroxyprogesterone and 11-deoxycortisol, for
example; as a result, cortisol values may be artifactually increased in patients
with congenital adrenal hyperplasia and adrenal carcinoma or after",
" <a class=\"drug drug_general\" href=\"UTD.htm?15/12/15556?source=see_link\">",
" metyrapone",
" </a>",
" administration. Some radioimmunoassays are more specific. Cortisol can be
chromatographically separated from other steroids before assay in these situations
[",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/43\">",
" 43",
" </a>",
" ].",
" </p>",
" <p>",
" More recently, developments of liquid chromatography mass spectrometry methods
with less cross-reactivity than antibody-based methods, may yield fewer false
positive results when used for the diagnosis of Cushing's syndrome [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/50\">",
" 50",
" </a>",
" ].",
" </p>",
" <p>",
" Measuring salivary cortisol is especially useful in assessing cortisol
secretion serially in ambulatory patients, who can collect multiple samples and
store them in a refrigerator or freezer or even at room temperature for several
days between clinic visits. They are also helpful in the evaluation of patients
suspected of having cyclical Cushing's syndrome [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/132/abstract/45,51-54\">",
" 45,51-54",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?21/25/21913?
source=see_link\">",
" \"Establishing the diagnosis of Cushing's syndrome\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H32\">",
" <span class=\"h1\">",
" SUMMARY",
" </span>",
" &nbsp;&mdash;&nbsp;Measurement of total, free, and salivary cortisol has been
advocated for the assessment of adrenal function. The results are affected by the
following factors:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" The assay methodology affects the normal range. Currently available
antibody-based assays cross react with non-cortisol steroids and have a higher
upper limit of normal than structurally-based assays such as high pressure liquid
chromatography.",
" </li>",
" <li>",
" Changes in CBG and albumin, the binding proteins for cortisol, affect total
serum levels, but not free levels in the serum or saliva. These proteins may be
substantially reduced in critically ill patients, so that total cortisol values may
not reflect adrenal function. Conversely, estrogen-induced increases in CBG may
mask low cortisol production.",
" </li>",
" </ul>",
" </p>",
" <p>",
" In individuals with normal sleep-wake cycles, cortisol values are lowest
around bedtime, and peak in the early morning. This physiologic difference has been
used for diagnostic purposes:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Patients with Cushing's syndrome have elevated late night salivary and serum
cortisol values. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?21/25/21913?
source=see_link\">",
" \"Establishing the diagnosis of Cushing's syndrome\"",
" </a>",
" .)",
" </li>",
" <li>",
" Patients with severe adrenal insufficiency may have low early morning serum
cortisol concentrations. If the value is greater than 10",
" <span class=\"nowrap\">",
" mcg/dL",
" </span>",
" (276",
" <span class=\"nowrap\">",
" nmol/L),",
" </span>",
" it is unlikely that the patient has clinically important adrenal
insufficiency, whereas if it is less than 3",
" <span class=\"nowrap\">",
" mcg/dL",
" </span>",
" (83",
" <span class=\"nowrap\">",
" nmol/L),",
" </span>",
" the probability of adrenal insufficiency is high.",
" </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>",
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" </a>",
" </li>",
" </ol>",
" </div>",
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var outline_f0_8_132=[" <div id=\"toggleOutline\">",
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" <div id=\"innerOutline\">",
" <h1>",
" TOPIC OUTLINE",
" </h1>",
" <div id=\"outline\">",
" <ul>",
" <li>",
" <a class=\"sr_button\" href=\"#H32\" id=\"summRecButton\">",
" <span>",
" SUMMARY",
" </span>",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H1\">",
" INTRODUCTION",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H2\">",
" MEASUREMENT OF SERUM CORTISOL",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H3\">",
" Methods of measurement",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H4\">",
" - Porter-Silber chromogens",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H5\">",
" - Competitive protein-binding assay",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H6\">",
" - Fluorometric assay",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H7\">",
" - Radioreceptor assay",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H8\">",
" - Radioimmunoassay",
" </a>",
" </li>",
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" <a class=\"outlineLink\" href=\"#H9\">",
" - Other immunoassays",
" </a>",
" </li>",
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" <a class=\"outlineLink\" href=\"#H10\">",
" - Structurally-based assays",
" </a>",
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" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H11\">",
" Normal values",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H12\">",
" Interpretation",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H13\">",
" Important caveats",
" </a>",
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" <a class=\"outlineLink\" href=\"#H14\">",
" - CBG",
" </a>",
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" - Hepatic and renal dysfunction",
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" - Thyroid hormone",
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" - Body weight",
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" - Age",
" </a>",
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" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H19\">",
" - Depression",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H20\">",
" - Synthetic glucocorticoids",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H21\">",
" - Non-glucocorticoid drugs",
" </a>",
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" - Alcohol abuse",
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" SERUM FREE CORTISOL",
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" <a class=\"outlineLink\" href=\"#H25\">",
" CORTISOL PRECURSORS",
" </a>",
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" <a class=\"outlineLink\" href=\"#H26\">",
" Normal values",
" </a>",
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" <a class=\"outlineLink\" href=\"#H27\">",
" Interpretation",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H28\">",
" MEASUREMENT OF SALIVARY CORTISOL CONCENTRATION",
" </a>",
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" Assay",
" </a>",
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" <a class=\"outlineLink\" href=\"#H30\">",
" Normal values",
" </a>",
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" Interpretation",
" </a>",
" </li>",
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" <a class=\"outlineLink\" href=\"#H32\">",
" SUMMARY",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#references\">",
" REFERENCES",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" <div class=\"openRelatedGraphics\" id=\"ENDO/161\" rel=\"outline_link\">",
" GRAPHICS",
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" <a href=\"#\" title=\"FIGURES\">",
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" </div>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_figure\" href=\"UTD.htm?6/17/6431\" title=\"figure
1\">",
" Circadian rhythm of plasma ACTH",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_figure\" href=\"UTD.htm?36/46/37614\"
title=\"figure 2\">",
" Circadian rhythm in serum cortisol",
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1\">",
" Normal salivary cortisol",
" </a>",
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" </div>",
" <h1>",
" RELATED TOPICS",
" </h1>",
" <div id=\"relatedTopics\">",
" <ul>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?43/46/44777?
source=related_link\">",
" Diagnosis of adrenal insufficiency in adults",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?21/25/21913?
source=related_link\">",
" Establishing the diagnosis of Cushing's syndrome",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?24/20/24905?
source=related_link\">",
" Evaluation of the response to ACTH in adrenal insufficiency",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?21/37/22103?
source=related_link\">",
" Glucocorticoid withdrawal",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?15/48/16135?
source=related_link\">",
" Metyrapone stimulation tests",
" </a>",
" </li>",
" </ul>",
" </div>",
" </div>"].join("\n");
var title_f0_8_133="Pathogenesis, clinical manifestations, and diagnosis of morphea
(localized scleroderma) in adults";
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" Pathogenesis, clinical manifestations, and diagnosis of morphea (localized
scleroderma) in adults",
" </div>",
" <div id=\"topicContributors\">",
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" <a id=\"authors\">",
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" Author",
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0/8/133/contributors\">",
" Heidi Jacobe, MD",
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href=\"UTD.htm?0/8/133/contributors\">",
" Section Editor",
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" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/8/133/contributors\">",
" Jeffrey Callen, MD, FACP, FAAD",
" </a>",
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href=\"UTD.htm?0/8/133/contributors\">",
" Deputy Editor",
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0/8/133/contributors\">",
" Abena O Ofori, MD",
" </a>",
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" Literature review current through:",
" </span>",
" Oct 2013.",
" <span class=\"pipeSpace\">",
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" Jan 20, 2012.",
" </div>",
" <div id=\"topicText\">",
" <p class=\"headingAnchor\" id=\"H16539042\">",
" <span class=\"h1\">",
" INTRODUCTION",
" </span>",
" &nbsp;&mdash;&nbsp;Morphea, also known as localized scleroderma, is an
idiopathic, often self-limited, inflammatory disorder that causes fibrotic changes
in the skin. Morphea is distinct from systemic sclerosis (scleroderma), an
autoimmune connective tissue disorder characterized by acral or diffuse cutaneous
sclerosis and frequent systemic manifestations. Use of the term morphea diminishes
the likelihood of confusion between these two disorders, which can lead to
unnecessary patient anxiety. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?28/34/29224?
source=see_link\">",
" \"Overview of the clinical manifestations of systemic sclerosis (scleroderma)
in adults\"",
" </a>",
" .)",
" </p>",
" <p>",
" Patients with morphea present with single or multiple inflammatory or
sclerotic plaques. Disease activity typically persists for three to six years; a
minority of patients develop more persistent or recurring involvement. Cosmetic
disfigurement or functional impairments due to atrophy or contractures often remain
after the resolution of active disease. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?17/14/17640?
source=see_link&amp;anchor=H20781968#H20781968\">",
" \"Treatment of morphea (localized scleroderma) in adults\", section on
'Prognosis'",
" </a>",
" .)",
" </p>",
" <p>",
" The epidemiology, pathogenesis, clinical manifestations, and diagnosis of
morphea in adults will be reviewed here. The treatment and prognosis of morphea in
adults and the features and management of morphea in children are discussed
elsewhere. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?40/1/40985?
source=see_link\">",
" \"Localized scleroderma in childhood\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H16539049\">",
" <span class=\"h1\">",
" EPIDEMIOLOGY",
" </span>",
" &nbsp;&mdash;&nbsp;Morphea is a relatively uncommon disorder that affects
adults and children [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/1-4\">",
" 1-4",
" </a>",
" ]. The annual incidence of morphea was approximately 3 per 100,000 people in a
population in the United States between 1960 and 1993 [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/5\">",
" 5",
" </a>",
" ].",
" </p>",
" <p>",
" Although morphea can occur at any age, many patients (50 to 65 percent)
develop the disease as adults [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/4,5\">",
" 4,5",
" </a>",
" ]. In one retrospective study of 82 patients with morphea, the mean age of
diagnosis was 33 years. Females are more susceptible; in the same study, the female
to male ratio was 2.6 to 1 [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/5\">",
" 5",
" </a>",
" ].",
" </p>",
" <p>",
" Ethnicity also may influence the risk for morphea. The results of
retrospective studies suggest that the disorder may be more common in Caucasians
and may occur at a lower than expected frequency in African-Americans [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/3,4\">",
" 3,4",
" </a>",
" ]. Additional studies are necessary to confirm these findings.",
" </p>",
" <p class=\"headingAnchor\" id=\"H16539056\">",
" <span class=\"h1\">",
" PATHOGENESIS",
" </span>",
" &nbsp;&mdash;&nbsp;The pathogenesis of morphea is poorly understood. Theories
on the pathogenesis of morphea are often extrapolated from studies of systemic
sclerosis [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/6\">",
" 6",
" </a>",
" ]. A variety of factors, including autoimmunity, genetics, and vascular
dysfunction may play a role in morphea. Multiple environmental factors (eg,
infections or environmental exposures) also have been proposed as contributors to
disease expression. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?40/1/40985?
source=see_link&amp;anchor=H5#H5\">",
" \"Localized scleroderma in childhood\", section on 'Etiology'",
" </a>",
" .)",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" <strong>",
" Immune dysfunction &mdash;",
" </strong>",
" It is generally accepted that immune dysfunction is involved in the
development of morphea [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/4,7,8\">",
" 4,7,8",
" </a>",
" ]. A role for autoimmunity in the development of this disorder is supported
by the following:",
" </li>",
" </ul>",
" </p>",
" <p>",
" <ul class=\"hyphen-block\">",
" <li>",
" A clinically evident inflammatory stage often precedes the development of
sclerosis [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/9\">",
" 9",
" </a>",
" ].",
" </li>",
" <li>",
" Histopathologic studies of early lesions demonstrate an influx of large
numbers of mononuclear lymphocytes (primarily activated T lymphocytes), plasma
cells, and eosinophils [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/6\">",
" 6",
" </a>",
" ].",
" </li>",
" <li>",
" Cytokines associated with Th2 immune responses, such as interleukin (IL)-4,
are detected at increased levels in patients with morphea [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/10\">",
" 10",
" </a>",
" ]. IL-4 produced by CD4+ Th2 lymphocytes can upregulate the production of
transforming growth factor (TGF)-beta by T lymphocytes and other cells [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/6\">",
" 6",
" </a>",
" ]. TGF-beta is capable of stimulating fibroblast production of collagen and
other extracellular matrix proteins.",
" </li>",
" <li>",
" Increased autoantibody levels are present in some patients with morphea,
particularly those with the generalized or linear variants [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/4,7,8\">",
" 4,7,8",
" </a>",
" ].",
" </li>",
" </ul>",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" <strong>",
" Vascular dysfunction &ndash;",
" </strong>",
" The detection of reduced numbers of dermal capillaries, abnormalities in
basal lamina of blood vessels, and endothelial cell damage in specimens from
lesional skin support a role for vascular dysfunction in the development of morphea
[",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/11\">",
" 11",
" </a>",
" ].",
" <br/>",
" <br/>",
" One theory of the pathogenesis of morphea proposes that injury to the
vascular endothelium during the inflammatory stage stimulates the release of
cytokines that upregulate the expression of vascular adhesion molecules, including
vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1
(ICAM-1), and E-selectin [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/6,11\">",
" 6,11",
" </a>",
" ]. These adhesion molecules facilitate the recruitment of T-lymphocytes that
are capable of producing profibrotic cytokines (IL-4, IL-6, and TGF-beta), and may
contribute to the development to sclerosis [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/6,11\">",
" 6,11",
" </a>",
" ]. Of note, increased levels of vascular adhesion molecules have been
detected in serum from patients with morphea [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/12\">",
" 12",
" </a>",
" ].",
" </li>",
" <li>",
" <strong>",
" Genetics &ndash;",
" </strong>",
" Although susceptibility genes for the development of morphea have not been
identified, reports of familial case clusters [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/4,13,14\">",
" 4,13,14",
" </a>",
" ] and the detection of increased rates of autoimmune disorders in family
members of patients with morphea [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/4,7,15\">",
" 4,7,15",
" </a>",
" ] suggest a genetic contribution.",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H16539063\">",
" <span class=\"h1\">",
" CLINICAL MANIFESTATIONS",
" </span>",
" &nbsp;&mdash;&nbsp;Morphea is divided into several subtypes [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/16\">",
" 16",
" </a>",
" ], all of which transition through an early inflammatory stage followed by
sclerosis and subsequent atrophy (",
" <a class=\"graphic graphic_figure graphicRef70565 \" href=\"UTD.htm?
2/18/2343\">",
" figure 1",
" </a>",
" ). The depth of involvement may be superficial (primarily dermal) or deep
(involving the deep dermis plus the subcutis, fascia,",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" bone).",
" </p>",
" <p class=\"headingAnchor\" id=\"H1477944\">",
" <span class=\"h2\">",
" Lesion evolution",
" </span>",
" &nbsp;&mdash;&nbsp;Sclerotic lesions in the skin manifest as firm, bound-down
plaques or nodules. However, in morphea, the initial sign of disease is often an
inflammatory, erythematous patch or edematous plaque. Some patients may note
unexplained pain or itching at the site of disease prior to the development of a
clinically evident lesion. Sclerosis usually begins in the center of inflammatory
lesions, initially leaving an erythematous or violaceous border (",
" <a class=\"graphic graphic_picture graphicRef73769 graphicRef57586 \"
href=\"UTD.htm?36/56/37764\">",
" picture 1A-B",
" </a>",
" ). Hypopigmentation, hyperpigmentation, alopecia secondary to loss of hair
follicles, and a shiny cutaneous surface are common additional features of
sclerotic lesions (",
" <a class=\"graphic graphic_picture graphicRef62452 \" href=\"UTD.htm?
2/52/2883\">",
" picture 7B",
" </a>",
" ).",
" </p>",
" <p>",
" After a period of months to years, sclerotic plaques soften and transition
into hypopigmented or hyperpigmented atrophic plaques (",
" <a class=\"graphic graphic_picture graphicRef70426 \" href=\"UTD.htm?
5/43/5823\">",
" picture 6B",
" </a>",
" ). Atrophy in lesions that primarily involve the dermis may present as areas
of fine, cigarette-paper like skin or shallow (cliff drop-like) depressions.
Patients with deep morphea, which extends into the subcutis and beyond, may be left
with deep indentations after the resolution of active disease.",
" </p>",
" <p class=\"headingAnchor\" id=\"H1143130\">",
" <span class=\"h2\">",
" Variants",
" </span>",
" &nbsp;&mdash;&nbsp;There is a lack of consensus on the appropriate
classification system for morphea [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/11,16\">",
" 11,16",
" </a>",
" ]. We prefer the clinically-based division of morphea into circumscribed,
generalized, linear, and mixed forms (",
" <a class=\"graphic graphic_table graphicRef56238 \" href=\"UTD.htm?
12/61/13276\">",
" table 1",
" </a>",
" ).",
" </p>",
" <p>",
" Circumscribed lesions are the most common manifestation of morphea in adults,
and like the generalized variant, are more frequently observed in adults than in
children. Linear morphea is the most common subtype of morphea in children [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/1,3-5,17-19\">",
" 1,3-5,17-19",
" </a>",
" ]. Less common variants of morphea include guttate, bullous, and keloidal
disease. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?40/1/40985?
source=see_link&amp;anchor=H6#H6\">",
" \"Localized scleroderma in childhood\", section on 'Clinical
manifestations'",
" </a>",
" .)",
" </p>",
" <p>",
" Studies conflict on the relative frequency of morphea subtypes; differences in
classification criteria likely contribute to the discrepant results. A
retrospective study of 113 adults with morphea found the following frequencies of
clinical variants [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/18\">",
" 18",
" </a>",
" ]:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Circumscribed ��� 65 percent",
" </li>",
" <li>",
" Generalized ��� 8 percent",
" </li>",
" <li>",
" Linear ��� 6 percent",
" </li>",
" <li>",
" En coup de sabre (a form of linear disease) ��� 3.5 percent",
" </li>",
" <li>",
" Deep (morphea profunda) ��� 3.5 percent",
" </li>",
" <li>",
" Guttate or bullous ��� less than 1 percent each",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H16539070\">",
" <span class=\"h3\">",
" Circumscribed (plaque) morphea",
" </span>",
" &nbsp;&mdash;&nbsp;Circumscribed morphea, also known as plaque morphea,
presents as single or multiple, well-defined, oval to round plaques that fail to
meet criteria for generalized morphea (",
" <a class=\"graphic graphic_picture graphicRef73769 graphicRef53822
graphicRef63984 \" href=\"UTD.htm?0/14/234\">",
" picture 1A, 1C-D",
" </a>",
" ). In some patients, linear or generalized morphea initially presents with
features consistent with circumscribed disease. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?40/1/40985?
source=see_link&amp;anchor=H7#H7\">",
" \"Localized scleroderma in childhood\", section on 'Circumscribed (plaque)
morphea'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H10098186\">",
" <span class=\"h4\">",
" Deep morphea",
" </span>",
" &nbsp;&mdash;&nbsp;Deep morphea, or morphea profunda, is a form of
circumscribed morphea that primarily involves the deep dermis and subcutaneous
tissue and may extend to underlying fascia and muscle. Plaques are poorly
circumscribed and often occur in a symmetrical distribution (",
" <a class=\"graphic graphic_picture graphicRef77587 \" href=\"UTD.htm?
27/57/28561\">",
" picture 2",
" </a>",
" ). Clinical examination reveals lesions that have an indurated texture and
feel tightly tethered to underlying fascia and muscle. Linear areas of depression
(the &ldquo;groove sign&rdquo;) may be present at sites with underlying tendons and
ligaments. Other forms of morphea, particularly linear and generalized morphea, may
also demonstrate involvement of deep tissues.",
" </p>",
" <p class=\"headingAnchor\" id=\"H1143309\">",
" <span class=\"h3\">",
" Generalized morphea",
" </span>",
" &nbsp;&mdash;&nbsp;Generalized morphea is defined by the presence of &ge;4
morpheaform plaques involving at least two different anatomic sites (",
" <a class=\"graphic graphic_picture graphicRef56113 graphicRef68904 \"
href=\"UTD.htm?36/45/37587\">",
" picture 3A-B",
" </a>",
" ) [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/11\">",
" 11",
" </a>",
" ]. In contrast to systemic sclerosis, generalized morphea does not present
with sclerosis primarily involving acral skin or sclerodactyly. Lesions of
generalized morphea frequently begin on the trunk before spreading acrally, and the
fingers and toes are spared. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?28/34/29224?
source=see_link\">",
" \"Overview of the clinical manifestations of systemic sclerosis (scleroderma)
in adults\"",
" </a>",
" .)",
" </p>",
" <p>",
" In the pansclerotic type of generalized morphea, deep morphea lesions occur in
a generalized, circumferential distribution and involve the majority of the body
surface area, excluding fingers and toes (",
" <a class=\"graphic graphic_picture graphicRef82198 \" href=\"UTD.htm?
2/22/2403\">",
" picture 4",
" </a>",
" ) [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/20,21\">",
" 20,21",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?40/1/40985?
source=see_link&amp;anchor=H8#H8\">",
" \"Localized scleroderma in childhood\", section on 'Generalized morphea'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H16539077\">",
" <span class=\"h3\">",
" Linear morphea",
" </span>",
" &nbsp;&mdash;&nbsp;Linear morphea (aka linear scleroderma) manifests as
morpheaform plaques arranged in a linear distribution. Lesions most frequently
occur on the extremities or face, but may also appear on the trunk, where the
differential diagnosis includes circumscribed morphea (",
" <a class=\"graphic graphic_picture graphicRef51218 graphicRef60348 \"
href=\"UTD.htm?15/10/15523\">",
" picture 5A-B",
" </a>",
" ). Patients may have single or multiple sites of involvement. The results of
one retrospective study of 65 children with linear morphea suggested that linear
morphea can follow the lines of Blaschko [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/22\">",
" 22",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?40/1/40985?
source=see_link&amp;anchor=H9#H9\">",
" \"Localized scleroderma in childhood\", section on 'Linear scleroderma'",
" </a>",
" .)",
" </p>",
" <p>",
" Involvement of deep tissues (subcutaneous tissue, muscle, or bone) in linear
morphea can lead to significant deformities, including muscle weakness, joint
contractures, and in growing children, limb length discrepancies (",
" <a class=\"graphic graphic_picture graphicRef55660 graphicRef70426 \"
href=\"UTD.htm?27/1/27665\">",
" picture 6A-B",
" </a>",
" ). Bone marrow inflammation has also been reported in patients with linear
morphea [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/23,24\">",
" 23,24",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H1143389\">",
" <span class=\"h4\">",
" En coup de sabre",
" </span>",
" &nbsp;&mdash;&nbsp;En coup de sabre is a type of linear morphea that affects
the head and neck. Lesions manifest as hyperpigmented atrophic plaques that
resemble the cut of a sword (",
" <a class=\"graphic graphic_picture graphicRef75258 graphicRef62452
graphicRef73173 graphicRef80877 \" href=\"UTD.htm?21/10/21674\">",
" picture 7A-D",
" </a>",
" ). The forehead is the most common site of involvement; lesions may extend
onto the scalp, where they cause permanent alopecia. Other classic sites of
involvement include the temple and chin. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?40/1/40985?
source=see_link&amp;anchor=H10#H10\">",
" \"Localized scleroderma in childhood\", section on 'Linear scleroderma of the
face'",
" </a>",
" .)",
" </p>",
" <p>",
" It is controversial whether progressive facial hemiatrophy (Parry-Romberg
syndrome), which is characterized by unilateral atrophy of the skin, soft tissues,
muscles,",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" bones of the face, is a variant of linear morphea or an independent disorder
(",
" <a class=\"graphic graphic_picture graphicRef70253 \" href=\"UTD.htm?
16/4/16450\">",
" picture 8",
" </a>",
" ). In this condition, facial atrophy may be accompanied by classic linear
morphea lesions on the face or elsewhere. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?40/1/40985?
source=see_link&amp;anchor=H10#H10\">",
" \"Localized scleroderma in childhood\", section on 'Linear scleroderma of the
face'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H10098200\">",
" <span class=\"h3\">",
" Mixed morphea",
" </span>",
" &nbsp;&mdash;&nbsp;Mixed morphea is a term used to describe the simultaneous
presence of more than one subtype.",
" </p>",
" <p class=\"headingAnchor\" id=\"H1477951\">",
" <span class=\"h2\">",
" Extracutaneous manifestations",
" </span>",
" &nbsp;&mdash;&nbsp;Disorders of the musculoskeletal system (arthralgias, joint
swelling, myalgias, limb contractures, and limited range of motion) can occur in
patients with morphea (",
" <a class=\"graphic graphic_picture graphicRef55031 \" href=\"UTD.htm?
11/22/11616\">",
" picture 9",
" </a>",
" ) [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/4\">",
" 4",
" </a>",
" ]. Adults with generalized or deep morphea may be more likely than other
affected adults to experience musculoskeletal symptoms [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/18\">",
" 18",
" </a>",
" ]. Raynaud&rsquo;s phenomenon also has been reported in a minority of children
and adults with morphea [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/4,18\">",
" 4,18",
" </a>",
" ].",
" </p>",
" <p>",
" Pulmonary and esophageal abnormalities occur in a minority of patients with
morphea; however, in the vast majority of cases, this has been asymptomatic and
only detectable with investigational tests [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/25\">",
" 25",
" </a>",
" ]. Occasionally, symptoms of dysphagia or dyspnea may develop secondary to the
restrictive effects of extensive cutaneous sclerosis. Evaluation for pulmonary or
esophageal abnormalities is not indicated in the absence of symptoms.",
" </p>",
" <p>",
" Approximately 4 percent of children with en coup de sabre have neurologic or
ocular complications, including seizures, headaches, uveitis, episcleritis, and
adnexal abnormalities involving the eyelids, eyelashes, or lacrimal glands; the
proportion of adults with these findings is uncertain [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/15,26-28\">",
" 15,26-28",
" </a>",
" ]. En coup de sabre or other lesions involving the face also may produce
dental malocclusion, altered dentition, and atrophy of tongue and salivary glands.
The approach to patients with suspected joint, neurologic, ocular, or oral
involvement is discussed separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?17/14/17640?
source=see_link&amp;anchor=H20781940#H20781940\">",
" \"Treatment of morphea (localized scleroderma) in adults\", section on 'Other
interventions'",
" </a>",
" .)",
" </p>",
" <p>",
" Other autoimmune disorders may occur at a relatively high frequency in
patients with morphea. In a study of 123 adults with this disorder, 37 (30 percent)
had another autoimmune disease. Concomitant autoimmune disease was most common in
adults with generalized morphea [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/4\">",
" 4",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H16539105\">",
" <span class=\"h1\">",
" DIAGNOSIS",
" </span>",
" &nbsp;&mdash;&nbsp;In many patients, the diagnosis of morphea can be made
based upon the clinical findings. However, histopathologic studies and radiologic
imaging can be useful to confirm a diagnosis or evaluate the extent of disease. A
diagnostic algorithm for patients with clinical features suggestive of morphea is
provided (",
" <a class=\"graphic graphic_algorithm graphicRef62195 \" href=\"UTD.htm?
24/20/24911\">",
" algorithm 1",
" </a>",
" ).",
" </p>",
" <p class=\"headingAnchor\" id=\"H8784295\">",
" <span class=\"h2\">",
" Histopathology",
" </span>",
" &nbsp;&mdash;&nbsp;Tissue biopsies are generally reserved for cases in which
the diagnosis is in question. All biopsy specimens should include subcutaneous fat.
A punch biopsy that extends into the subcutaneous fat can be performed in
superficial lesions of morphea. In cases of deep involvement, a punch biopsy is
unlikely to reach sufficient depth, and an incisional biopsy should be performed.",
" </p>",
" <p>",
" The biopsy specimen can be taken from the inflammatory or indurated border if
present, or from a central sclerotic area. The pathologist should be informed of
the clinical features of the site from which the biopsy is taken. For lesions with
minimal clinical change, a second biopsy from unaffected skin in a location similar
to the lesion site (eg, contralateral skin) should be performed to assist with
interpretation of the lesional pathologic findings.",
" </p>",
" <p>",
" The pathology of morphea varies based upon biopsy site, lesion stage, and
lesion depth. Biopsies performed from inflammatory lesions demonstrate an
interstitial and perivascular inflammatory cell infiltrate composed primarily of
lymphocytes and plasma cells. Eosinophils, mast cells, and macrophages may be
present. Inflammation may extend into the subcutaneous tissues. In addition, tissue
edema, enlarged tortuous vessels, and thickened collagen bundles may be observed.",
" </p>",
" <p>",
" As sclerosis progresses, lesions demonstrate homogenization of the papillary
dermis and thickened collagen bundles extending into the reticular dermis or beyond
(",
" <a class=\"graphic graphic_picture graphicRef76952 \" href=\"UTD.htm?
24/50/25383\">",
" picture 10",
" </a>",
" ). Fat surrounding eccrine glands diminishes, and advanced sclerotic lesions
exhibit compression and loss of appendageal structures. Few blood vessels are
present, and those that remain exhibit fibrotic walls and narrowed lumina. In
specimens from deep morphea, the deep reticular dermis, subcutis, and fascia show
sclerotic changes.",
" </p>",
" <p>",
" The atrophic phase of morphea is characterized by loss of inflammatory cell
infiltrate, less sclerosis, and an absence of appendageal structures.
Telangiectasia may be evident.",
" </p>",
" <p class=\"headingAnchor\" id=\"H16539112\">",
" <span class=\"h2\">",
" Serum autoantibodies",
" </span>",
" &nbsp;&mdash;&nbsp;Between 39 and 80 percent of adults and children with
morphea have elevated antinuclear antibody (ANA) levels [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/4,8,18,29\">",
" 4,8,18,29",
" </a>",
" ]. Elevations occur most commonly in patients with linear or generalized
morphea. Other autoantibodies occasionally detected in patients with morphea
include anti-single-stranded DNA (ssDNA), anti-double-stranded DNA (dsDNA),
antihistone, anti-topoisomerase II&alpha;, antiphospholipid, and rheumatoid factor
[",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/4,8,29-35\">",
" 4,8,29-35",
" </a>",
" ].",
" </p>",
" <p>",
" The clinical and prognostic significance of autoantibodies in morphea remains
unclear. Thus, testing for autoantibodies is not indicated in the absence of
clinical signs that suggest the presence of another autoimmune disorder.",
" </p>",
" <p class=\"headingAnchor\" id=\"H16539119\">",
" <span class=\"h2\">",
" Other serum abnormalities",
" </span>",
" &nbsp;&mdash;&nbsp;Peripheral eosinophilia, hypergammaglobulinemia, and
increased erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels
may occur with active disease of any type. Based upon our observations, when
eosinophilia is present in patients with deep morphea, the level of eosinophilia
may correlate with disease activity. This finding may reflect the overlapping
features of deep morphea and eosinophilic fasciitis. (See",
" <a class=\"local\" href=\"#H8784283\">",
" 'Eosinophilic fasciitis'",
" </a>",
" below.) &nbsp;",
" </p>",
" <p class=\"headingAnchor\" id=\"H16539126\">",
" <span class=\"h2\">",
" Imaging studies",
" </span>",
" &nbsp;&mdash;&nbsp;In patients who present with clinical findings that suggest
morphea that extends beyond the dermis (eg, tightly bound-down quality on skin
examination, muscle weakness, contractures, or limb length discrepancies), magnetic
resonance imaging (MRI) should be used to assess lesion depth and involvement of
subcutaneous structures [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/24,36\">",
" 24,36",
" </a>",
" ]. Ultrasonography is an alternative to MRI [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/37\">",
" 37",
" </a>",
" ].",
" </p>",
" <p>",
" MRI and ultrasound have also been used to monitor disease activity [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/24,38\">",
" 24,38",
" </a>",
" ]. With both modalities, discussion with the radiologist is essential to
correlate the radiologic findings with clinical disease.",
" </p>",
" <p class=\"headingAnchor\" id=\"H8784262\">",
" <span class=\"h1\">",
" DIFFERENTIAL DIAGNOSIS",
" </span>",
" &nbsp;&mdash;&nbsp;A number of other disorders can present with clinical
features that resemble morphea.",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" <strong>",
" Systemic sclerosis &ndash;",
" </strong>",
" Systemic sclerosis (scleroderma) is an autoimmune disorder characterized by
progressive sclerosis of the skin and frequent internal organ involvement. Unlike
morphea, sclerodactyly is a prominent feature in patients with systemic sclerosis.
(See",
" <a class=\"medical medical_review\" href=\"UTD.htm?28/34/29224?
source=see_link\">",
" \"Overview of the clinical manifestations of systemic sclerosis
(scleroderma) in adults\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?42/5/43095?
source=see_link&amp;anchor=H6#H6\">",
" \"Diagnosis and differential diagnosis of systemic sclerosis (scleroderma)
in adults\", section on 'Differential diagnosis'",
" </a>",
" .)",
" </li>",
" <li>",
" <strong>",
" Lipodermatosclerosis &ndash;",
" </strong>",
" Lipodermatosclerosis is a fibrosing panniculitis that usually occurs on the
lower legs in association with chronic venous insufficiency. Patients present with
indurated, sometimes circumferential plaques that may give the lower leg the
appearance of an inverted champagne bottle. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?13/17/13592?
source=see_link&amp;anchor=H14#H14\">",
" \"Clinical evaluation of lower extremity chronic venous disease\", section
on 'Lipodermatosclerosis'",
" </a>",
" .)",
" </li>",
" <li>",
" <strong>",
" Carcinoma en cuirasse and postirradiation morphea &ndash;",
" </strong>",
" Lesions involving the breast should be biopsied to exclude carcinoma en
cuirasse, a rare condition that occurs most frequently in the setting of breast
cancer. Tumor infiltrates skin and subcutaneous tissue, causing diffuse sclerotic
changes on the chest. Morpheaform changes in the breast also rarely occur as a
complication of radiation therapy (",
" <a class=\"graphic graphic_picture graphicRef67509 \" href=\"UTD.htm?
27/45/28383\">",
" picture 11",
" </a>",
" ) [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/39,40\">",
" 39,40",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?29/45/30426?
source=see_link&amp;anchor=H7#H7\">",
" \"Management of locoregional recurrence of breast cancer after
mastectomy\", section on 'Presenting signs and symptoms'",
" </a>",
" .)",
" </li>",
" </ul>",
" </p>",
" <p>",
" Additional disorders in the differential diagnosis are provided in a table (",
" <a class=\"graphic graphic_table graphicRef68996 \" href=\"UTD.htm?
0/14/236\">",
" table 2",
" </a>",
" ).",
" </p>",
" <p class=\"headingAnchor\" id=\"H8785559\">",
" <span class=\"h1\">",
" RELATED DISORDERS",
" </span>",
" </p>",
" <p class=\"headingAnchor\" id=\"H8784269\">",
" <span class=\"h2\">",
" Lichen sclerosus",
" </span>",
" &nbsp;&mdash;&nbsp;Clinical findings indicative of extragenital or genital
lichen sclerosus, conditions that usually manifest as atrophic white patches with
finely wrinkled surfaces, may occur in patients with morphea, particularly those
with circumscribed or generalized morphea [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/41\">",
" 41",
" </a>",
" ]. Extragenital lichen sclerosus most commonly occurs on the trunk and
proximal extremities (",
" <a class=\"graphic graphic_picture graphicRef82529 graphicRef74154
graphicRef58841 \" href=\"UTD.htm?25/56/26505\">",
" picture 12A-C",
" </a>",
" ). The labia minora, labia majora, glans penis, penile prepuce, and penile
foreskin are frequent sites for genital disease (",
" <a class=\"graphic graphic_picture graphicRef70014 graphicRef78530 \"
href=\"UTD.htm?7/27/7608\">",
" picture 13A-B",
" </a>",
" ). (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?28/17/28952?
source=see_link\">",
" \"Extragenital lichen sclerosus\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?6/45/6874?
source=see_link\">",
" \"Vulvar lichen sclerosus\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?14/33/14872?
source=see_link&amp;anchor=H16#H16\">",
" \"Balanitis and balanoposthitis in adults\", section on 'Lichen sclerosus or
balanitis xerotica obliterans'",
" </a>",
" .)",
" </p>",
" <p>",
" The relationship between lichen sclerosus and morphea remains controversial.
It is unclear whether the appearance of lesions consistent with lichen sclerosus
represents the simultaneous occurrence of two separate disorders or the development
of clinical findings that resemble lichen sclerosus in lesions of morphea.",
" </p>",
" <p class=\"headingAnchor\" id=\"H8784276\">",
" <span class=\"h2\">",
" Atrophoderma of Pasini and Pierini",
" </span>",
" &nbsp;&mdash;&nbsp;Atrophoderma of Pasini and Pierini is an idiopathic
disorder that presents with single or multiple well-demarcated depressed patches.
The areas of depression exhibit a cliff drop-like appearance. Lesions are usually
round or oval, ranging in size from a few centimeters to large, expansive lesions.
The trunk is most commonly involved, and lesions tend to have a symmetrical
distribution.",
" </p>",
" <p>",
" The relationship between atrophoderma of Pasini and Pierini and morphea is
unclear. Atrophoderma of Pasini and Pierini may represent the atrophic stage of
plaque-type morphea, or may be a separate disorder.",
" </p>",
" <p class=\"headingAnchor\" id=\"H8784283\">",
" <span class=\"h2\">",
" Eosinophilic fasciitis",
" </span>",
" &nbsp;&mdash;&nbsp;Eosinophilic fasciitis, or Shulman syndrome, is a disorder
that is characterized by the rapid onset of symmetric, painful, large, edematous
plaques that evolve into fibrotic lesions. Some cases appear to be precipitated by
trauma. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?8/10/8360?
source=see_link\">",
" \"Eosinophilic fasciitis\"",
" </a>",
" .)",
" </p>",
" <p>",
" The extremities are the most common sites of involvement. Similar to deep
morphea, linear depressions (the &ldquo;groove sign&rdquo;) may be present in
involved areas. Laboratory abnormalities include peripheral eosinophilia,
hypergammaglobulinemia, and an elevated erythrocyte sedimentation rate (ESR).",
" </p>",
" <p>",
" A history of sudden onset plus histopathologic findings demonstrating a
characteristic marked thickening of the fascia accompanied by a mixed inflammatory
infiltrate with lymphocytes, histiocytes, plasma cells, and eosinophils may help to
distinguish this disorder from deep morphea. However, in some cases, the disorders
cannot be distinguished [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/42\">",
" 42",
" </a>",
" ]. Clinical findings consistent with morphea and eosinophilic fasciitis may
also coexist [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/133/abstract/43-45\">",
" 43-45",
" </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",
" ^{",
" th",
"}",
" to 6",
" ^{",
" th",
"}",
" 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",
" ^{",
" th",
"}",
" to 12",
" ^{",
" th",
"}",
" 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 topics (see",
" <a class=\"medical medical_basics\" href=\"UTD.htm?27/23/28017?
source=see_link\">",
" \"Patient information: Scleroderma (The Basics)\"",
" </a>",
" )",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H16539219\">",
" <span class=\"h1\">",
" SUMMARY AND RECOMMENDATIONS",
" </span>",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Morphea, also known as localized scleroderma, is a relatively uncommon
idiopathic inflammatory disorder that leads to the development of sclerotic plaques
in the skin. The disorder occurs in both adults and children and preferentially
affects females. (See",
" <a class=\"local\" href=\"#H16539049\">",
" 'Epidemiology'",
" </a>",
" above.)",
" </li>",
" <li>",
" The pathogenesis of morphea is not well understood. The disorder is likely
to have an autoimmune basis; genetic and environmental factors may also play a role
in the development of this disease. (See",
" <a class=\"local\" href=\"#H16539056\">",
" 'Pathogenesis'",
" </a>",
" above.)",
" </li>",
" <li>",
" Morphea has a variety of clinical presentations. Lesions of morphea
typically begin as inflammatory patches or plaques that evolve into firm, sclerotic
plaques. Involvement may be limited to the dermis, or may extend to underlying
subcutaneous fat, muscle, or bone. Atrophic changes often remain after lesion
resolution. (See",
" <a class=\"local\" href=\"#H16539063\">",
" 'Clinical manifestations'",
" </a>",
" above.)",
" </li>",
" <li>",
" The identification of characteristic clinical findings often is sufficient
for the diagnosis of morphea. Biopsy can be useful when the diagnosis is in
question or to obtain information on the depth of disease. Biopsies should always
extend at least into the subcutaneous fat. For sclerotic lesions, particularly
those with modest clinical change, a second biopsy from unaffected skin in a
similar location will assist with interpretation of the pathologic findings. (See",
" <a class=\"local\" href=\"#H16539105\">",
" 'Diagnosis'",
" </a>",
" above.)",
" </li>",
" <li>",
" Antinuclear antibody (ANA) levels are elevated in some patients with
morphea. However, the significance of this finding is unknown, and routine testing
for autoantibodies is not indicated in adults with morphea. (See",
" <a class=\"local\" href=\"#H16539112\">",
" 'Serum autoantibodies'",
" </a>",
" above.)",
" </li>",
" <li>",
" Radiologic imaging should be performed on patients in whom clinical
examination suggests the presence of morphea that extends deeper than the dermis
(",
" <a class=\"graphic graphic_algorithm graphicRef62195 \" href=\"UTD.htm?
24/20/24911\">",
" algorithm 1",
" </a>",
" ). Magnetic resonance imaging (MRI) or ultrasound can be used to assess the
extent of involvement and may be useful for following disease activity during
treatment. (See",
" <a class=\"local\" href=\"#H16539126\">",
" 'Imaging studies'",
" </a>",
" above.)",
" </li>",
" <li>",
" Morphea may cause joint contractures and other functional impairments
secondary to tissue sclerosis. All patients should be clinically assessed for the
development of these findings. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?17/14/17640?
source=see_link&amp;anchor=H20781940#H20781940\">",
" \"Treatment of morphea (localized scleroderma) in adults\", section on
'Other interventions'",
" </a>",
" .)",
" </li>",
" </ul>",
" </p>",
" <p>",
" <br/>",
" <strong>",
" </strong>",
" </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\">",
" <li>",
" Provost TT, Greenberg AS, Falanga V. Localized cutaneous sclerosis. In:
Cutaneous manifestations of rheumatic diseases, 1st ed, Sontheimer RD, Provost TT
(Eds), Williams &amp; Wilkins, Baltimore 1996. p.125.",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/2\">",
" Sehgal VN, Srivastava G, Aggarwal AK, et al. Localized scleroderma/morphea.
Int J Dermatol 2002; 41:467.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/3\">",
" Christen-Zaech S, Hakim MD, Afsar FS, Paller AS. Pediatric morphea
(localized scleroderma): review of 136 patients. J Am Acad Dermatol 2008; 59:385.",
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" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/4\">",
" Leitenberger JJ, Cayce RL, Haley RW, et al. Distinct autoimmune syndromes in
morphea: a review of 245 adult and pediatric cases. Arch Dermatol 2009; 145:545.",
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" </li>",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/5\">",
" Peterson LS, Nelson AM, Su WP, et al. The epidemiology of morphea (localized
scleroderma) in Olmsted County 1960-1993. J Rheumatol 1997; 24:73.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/6\">",
" Badea I, Taylor M, Rosenberg A, Foldvari M. Pathogenesis and therapeutic
approaches for improved topical treatment in localized scleroderma and systemic
sclerosis. Rheumatology (Oxford) 2009; 48:213.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/7\">",
" Saxton-Daniels S, Jacobe HT. An evaluation of long-term outcomes in adults
with pediatric-onset morphea. Arch Dermatol 2010; 146:1044.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/8\">",
" Takehara K, Moroi Y, Nakabayashi Y, Ishibashi Y. Antinuclear antibodies in
localized scleroderma. Arthritis Rheum 1983; 26:612.",
" </a>",
" </li>",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/9\">",
" Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. N Engl J Med 2009;
360:1989.",
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" </li>",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/10\">",
" Ihn H, Sato S, Fujimoto M, et al. Demonstration of interleukin-2,
interleukin-4 and interleukin-6 in sera from patients with localized scleroderma.
Arch Dermatol Res 1995; 287:193.",
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" </li>",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/11\">",
" Fett N, Werth VP. Update on morphea: part I. Epidemiology, clinical
presentation, and pathogenesis. J Am Acad Dermatol 2011; 64:217.",
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" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/12\">",
" Yamane K, Ihn H, Kubo M, et al. Increased serum levels of soluble vascular
cell adhesion molecule 1 and E-selectin in patients with localized scleroderma. J
Am Acad Dermatol 2000; 42:64.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/13\">",
" Wadud MA, Bose BK, Al Nasir T. Familial localised scleroderma from
Bangladesh: two case reports. Bangladesh Med Res Counc Bull 1989; 15:15.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/14\">",
" REES RB, BENNETT J. Localized scleroderma in father and daughter. AMA Arch
Derm Syphilol 1953; 68:360.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/15\">",
" Zulian F, Vallongo C, Woo P, et al. Localized scleroderma in childhood is
not just a skin disease. Arthritis Rheum 2005; 52:2873.",
" </a>",
" </li>",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/16\">",
" Laxer RM, Zulian F. Localized scleroderma. Curr Opin Rheumatol 2006;
18:606.",
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" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/17\">",
" Zulian F, Athreya BH, Laxer R, et al. Juvenile localized scleroderma:
clinical and epidemiological features in 750 children. An international study.
Rheumatology (Oxford) 2006; 45:614.",
" </a>",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/18\">",
" Marzano AV, Menni S, Parodi A, et al. Localized scleroderma in adults and
children. Clinical and laboratory investigations on 239 cases. Eur J Dermatol 2003;
13:171.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/19\">",
" Vierra E, Cunningham BB. Morphea and localized scleroderma in children.
Semin Cutan Med Surg 1999; 18:210.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/20\">",
" Patel AR, Pavletic SZ, Turner ML, Cowen EW. The isomorphic response in
morphealike chronic graft-vs-host disease. Arch Dermatol 2008; 144:1229.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/21\">",
" Minato H, Taki R, Miyachi Y, Utani A. Symmetrical pigmented sclerosis
enclosed by pruritic erythema: a new variant of morphoea? Br J Dermatol 2009;
161:703.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/22\">",
" Weibel L, Harper JI. Linear morphoea follows Blaschko's lines. Br J Dermatol
2008; 159:175.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/23\">",
" Muroi E, Ogawa F, Yamaoka T, et al. Case of localized scleroderma associated
with osteomyelitis. J Dermatol 2010; 37:81.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/24\">",
" Horger M, Fierlbeck G, Kuemmerle-Deschner J, et al. MRI findings in deep and
generalized morphea (localized scleroderma). AJR Am J Roentgenol 2008; 190:32.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/25\">",
" Dehen L, Roujeau JC, Cosnes A, Revuz J. Internal involvement in localized
scleroderma. Medicine (Baltimore) 1994; 73:241.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/26\">",
" Zulian F. New developments in localized scleroderma. Curr Opin Rheumatol
2008; 20:601.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/27\">",
" Tollefson MM, Witman PM. En coup de sabre morphea and Parry-Romberg
syndrome: a retrospective review of 54 patients. J Am Acad Dermatol 2007; 56:257.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/28\">",
" Zannin ME, Martini G, Athreya BH, et al. Ocular involvement in children with
localised scleroderma: a multi-centre study. Br J Ophthalmol 2007; 91:1311.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/29\">",
" Falanga V, Medsger TA Jr, Reichlin M. Antinuclear and anti-single-stranded
DNA antibodies in morphea and generalized morphea. Arch Dermatol 1987; 123:350.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/30\">",
" Rosenberg AM, Uziel Y, Krafchik BR, et al. Antinuclear antibodies in
children with localized scleroderma. J Rheumatol 1995; 22:2337.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/31\">",
" Sato S, Kodera M, Hasegawa M, et al. Antinucleosome antibody is a major
autoantibody in localized scleroderma. Br J Dermatol 2004; 151:1182.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/32\">",
" Sato S, Ihn H, Soma Y, et al. Antihistone antibodies in patients with
localized scleroderma. Arthritis Rheum 1993; 36:1137.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/33\">",
" Parodi A, Drosera M, Barbieri L, Rebora A. Antihistone antibodies in
scleroderma. Dermatology 1995; 191:16.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/34\">",
" Tomimura S, Ogawa F, Iwata Y, et al. Autoantibodies against matrix
metalloproteinase-1 in patients with localized scleroderma. J Dermatol Sci 2008;
52:47.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/35\">",
" Kroft EB, de Jong EM, Evers AW. Psychological distress in patients with
morphea and eosinophilic fasciitis. Arch Dermatol 2009; 145:1017.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/36\">",
" Schanz S, Fierlbeck G, Ulmer A, et al. Localized scleroderma: MR findings
and clinical features. Radiology 2011; 260:817.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/37\">",
" Li SC, Liebling MS, Haines KA. Ultrasonography is a sensitive tool for
monitoring localized scleroderma. Rheumatology (Oxford) 2007; 46:1316.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/38\">",
" Wortsman X, Wortsman J, Sazunic I, Carre&ntilde;o L. Activity assessment in
morphea using color Doppler ultrasound. J Am Acad Dermatol 2011; 65:942.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/39\">",
" Morganroth PA, Dehoratius D, Curry H, Elenitsas R. Postirradiation Morphea:
A Case Report With a Review of the Literature and Summary of the Clinicopathologic
Differential Diagnosis. Am J Dermatopathol 2010.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/40\">",
" Dubner S, Bovi J, White J, Susnik B. Postirradiation morphea in a breast
cancer patient. Breast J 2006; 12:173.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/41\">",
" Lutz V, Franc&egrave;s C, Bessis D, et al. High frequency of genital lichen
sclerosus in a prospective series of 76 patients with morphea: toward a better
understanding of the spectrum of morphea. Arch Dermatol 2012; 148:24.",
" </a>",
" </li>",
" <li>",
" Falanga V, Killoran CE. Morphea. In: Fitzpatrick's dermatology in general
medicine, 7th ed, Woff K, Goldsmith LA, Katz SI, et al. (Eds), McGraw-Hill, 2008.
p.543.",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/43\">",
" Castanet J, Lacour JP, Perrin C, et al. Association of eosinophilic
fasciitis, multiple morphea and antiphospholipid antibody. Dermatology 1994;
189:304.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/44\">",
" Heidary N, Cheung W, Wang N, et al. Eosinophilic fasciitis/generalized
morphea overlap. Dermatol Online J 2009; 15:2.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/133/abstract/45\">",
" Moulin C, Cavailhes A, Balme B, Skowron F. Morphoea-like plaques revealing
an eosinophilic (Shulman) fasciitis. Clin Exp Dermatol 2009; 34:e851.",
" </a>",
" </li>",
" </ol>",
" </div>",
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" <div id=\"innerOutline\">",
" <h1>",
" TOPIC OUTLINE",
" </h1>",
" <div id=\"outline\">",
" <ul>",
" <li>",
" <a class=\"sr_button\" href=\"#H16539219\" id=\"summRecButton\">",
" <span>",
" SUMMARY &amp; RECOMMENDATIONS",
" </span>",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H16539042\">",
" INTRODUCTION",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H16539049\">",
" EPIDEMIOLOGY",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H16539056\">",
" PATHOGENESIS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H16539063\">",
" CLINICAL MANIFESTATIONS",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H1477944\">",
" Lesion evolution",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H1143130\">",
" Variants",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H16539070\">",
" - Circumscribed (plaque) morphea",
" </a>",
" </li>",
" <li class=\"bulletItem2\">",
" <a class=\"outlineLink\" href=\"#H10098186\">",
" Deep morphea",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H1143309\">",
" - Generalized morphea",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H16539077\">",
" - Linear morphea",
" </a>",
" </li>",
" <li class=\"bulletItem2\">",
" <a class=\"outlineLink\" href=\"#H1143389\">",
" En coup de sabre",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H10098200\">",
" - Mixed morphea",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H1477951\">",
" Extracutaneous manifestations",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H16539105\">",
" DIAGNOSIS",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H8784295\">",
" Histopathology",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H16539112\">",
" Serum autoantibodies",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H16539119\">",
" Other serum abnormalities",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H16539126\">",
" Imaging studies",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H8784262\">",
" DIFFERENTIAL DIAGNOSIS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H8785559\">",
" RELATED DISORDERS",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H8784269\">",
" Lichen sclerosus",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H8784276\">",
" Atrophoderma of Pasini and Pierini",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H8784283\">",
" Eosinophilic fasciitis",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#PATIENT_INFORMATION\">",
" INFORMATION FOR PATIENTS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H16539219\">",
" SUMMARY AND RECOMMENDATIONS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#references\">",
" REFERENCES",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" <div class=\"openRelatedGraphics\" id=\"DERM/13776\" 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=\"DERM/13776|ALG\">",
" <a href=\"#\" title=\"ALGORITHMS\">",
" ALGORITHMS",
" </a>",
" </div>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_algorithm\" href=\"UTD.htm?24/20/24911\"
title=\"algorithm 1\">",
" Evaluation algorithm for morphea",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <div class=\"openRelatedGraphics\" id=\"DERM/13776|FIG\">",
" <a href=\"#\" title=\"FIGURES\">",
" FIGURES",
" </a>",
" </div>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_figure\" href=\"UTD.htm?2/18/2343\" title=\"figure
1\">",
" Morphea stages",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <div class=\"openRelatedGraphics\" id=\"DERM/13776|PIC\">",
" <a href=\"#\" title=\"PICTURES\">",
" PICTURES",
" </a>",
" </div>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?4/8/4225\"
title=\"picture 1A\">",
" Circumscribed morphea - inflammatory plaque",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?18/62/19439\"
title=\"picture 1B\">",
" Inflammatory morphea",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?8/16/8449\"
title=\"picture 1C\">",
" Circumscribed morphea - chest",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?12/6/12389\"
title=\"picture 1D\">",
" Circumscribed morphea - hyperpigmented plaque",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?27/57/28561\"
title=\"picture 2\">",
" Deep morphea",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?1/38/1632\"
title=\"picture 3A\">",
" Generalized morphea - trunk",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?25/40/26255\"
title=\"picture 3B\">",
" Generalized morphea - legs",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?2/22/2403\"
title=\"picture 4\">",
" Pansclerotic morphea",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?24/29/25041\"
title=\"picture 5A\">",
" Linear morphea",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?41/61/42973\"
title=\"picture 5B\">",
" Linear morphea - arm",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?37/33/38430\"
title=\"picture 6A\">",
" Linear morphea - limb abnormalities",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?5/43/5823\"
title=\"picture 6B\">",
" Atrophic morphea",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?25/21/25938\"
title=\"picture 7A\">",
" En coup de sabre - central forehead",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?2/52/2883\"
title=\"picture 7B\">",
" En coup de sabre - alopecia",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?12/26/12704\"
title=\"picture 7C\">",
" En coup de sabre - two examples",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?41/52/42816\"
title=\"picture 7D\">",
" En coup de sabre - face",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?16/4/16450\"
title=\"picture 8\">",
" Parry-Romberg syndrome",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?11/22/11616\"
title=\"picture 9\">",
" Arthritis in morphea",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?24/50/25383\"
title=\"picture 10\">",
" Morphea - histopathology",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?27/45/28383\"
title=\"picture 11\">",
" Postirradiation morphea",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?0/5/90\" title=\"picture
12A\">",
" Morphea and lichen sclerosus",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?26/37/27216\"
title=\"picture 12B\">",
" Lichen sclerosus - trunk",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?8/37/8789\"
title=\"picture 12C\">",
" Lichen sclerosus - histopathology",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?30/36/31299\"
title=\"picture 13A\">",
" LS adult 45 yrs",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?12/53/13138\"
title=\"picture 13B\">",
" Balanitis xerotica obliterans",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <div class=\"openRelatedGraphics\" id=\"DERM/13776|TAB\">",
" <a href=\"#\" title=\"TABLES\">",
" TABLES",
" </a>",
" </div>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?12/61/13276\" title=\"table
1\">",
" Classification of morphea",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?0/14/236\" title=\"table
2\">",
" Differential diagnosis of morphea",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" RELATED TOPICS",
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var title_f0_8_134="Clinical features, diagnosis, and treatment of Prader-Willi
syndrome";
var content_f0_8_134=[" <noscript>",
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" <div id=\"topicContent\">",
" <div id=\"topicTitle\">",
" Clinical features, diagnosis, and treatment of Prader-Willi syndrome",
" </div>",
" <div id=\"topicContributors\">",
" <div>",
" <a id=\"authors\">",
" </a>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?0/8/134/contributors\">",
" Author",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/8/134/contributors\">",
" Ann O Scheimann, MD, MBA",
" </a>",
" <br/>",
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href=\"UTD.htm?0/8/134/contributors\">",
" Section Editors",
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" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/8/134/contributors\">",
" William J Klish, MD",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/8/134/contributors\">",
" John L Kirkland, MD",
" </a>",
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" </div>",
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" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?0/8/134/contributors\">",
" Deputy Editor",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/8/134/contributors\">",
" Alison G Hoppin, MD",
" </a>",
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" </div>",
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" <span>",
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" </span>",
" <a href=\"/home/editorial-policy\" target=\"_blank\">",
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" </a>",
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" is complete.",
" </span>",
" </div>",
" <div id=\"literatureReviewDate\">",
" <span class=\"emphasis\">",
" Literature review current through:",
" </span>",
" Oct 2013.",
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" This topic last updated:",
" </span>",
" Jul 9, 2012.",
" </div>",
" <div id=\"topicText\">",
" <p class=\"headingAnchor\" id=\"H1\">",
" <span class=\"h1\">",
" INTRODUCTION",
" </span>",
" &nbsp;&mdash;&nbsp;Prader-Willi syndrome (PWS) is the most common syndromic
form of obesity. The syndrome is caused by absence of expression of the paternally
active genes on the long arm of chromosome 15. The vast majority of cases occur
sporadically.",
" </p>",
" <p>",
" The clinical features, diagnosis, and approaches to treatment of PWS will be
reviewed here. The epidemiology and genetics of this disorder are discussed
separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?16/8/16516?
source=see_link\">",
" \"Epidemiology and genetics of Prader-Willi syndrome\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H2\">",
" <span class=\"h1\">",
" CLINICAL MANIFESTATIONS",
" </span>",
" </p>",
" <p class=\"headingAnchor\" id=\"H3\">",
" <span class=\"h2\">",
" Prenatal",
" </span>",
" &nbsp;&mdash;&nbsp;Affected pregnancies often exhibit reduced fetal activity,
polyhydramnios, and breech positioning. Third-trimester ultrasounds may show
unusual positioning of the fetal hands and feet, with flexed wrists and dorsi-
extended feet with flexed toes [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/1\">",
" 1",
" </a>",
" ]. These abnormalities of limb positioning are supported only by case reports,
but are probably more specific than other ultrasound findings for Prader-Willi
syndrome (PWS). Cytogenetic examination is revealing only if specific molecular
diagnosis for PWS is requested. (See",
" <a class=\"local\" href=\"#H10\">",
" 'Genetic testing'",
" </a>",
" below.)",
" </p>",
" <p class=\"headingAnchor\" id=\"H4\">",
" <span class=\"h2\">",
" Infancy",
" </span>",
" &nbsp;&mdash;&nbsp;Neonatal hypotonia is one of the hallmark features of this
disorder and is a valuable clue to initiate diagnostic testing. The profound
hypotonia can lead to asphyxia. Affected infants often have feeding difficulties,
including a poor suck, which may lead to failure to thrive. Other common features
include a weak cry and genital hypoplasia (eg, cryptorchidism, scrotal hypoplasia,
or clitoral hypoplasia). Depigmentation of the skin or eyes relative to the
familial background is present in 30 to 50 percent of patients [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/2,3\">",
" 2,3",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H5\">",
" <span class=\"h2\">",
" Early childhood",
" </span>",
" &nbsp;&mdash;&nbsp;Toddlers with PWS demonstrate late acquisition of major
motor milestones. Children between one and six years of age commonly manifest
symptoms of hyperphagia with progressive development of obesity if access to food
is unrestricted. Body composition is abnormal, with reduced lean body mass and
increased fat mass as compared to normal and obese controls [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/4,5\">",
" 4,5",
" </a>",
" ]. Perhaps as a result of the reduced lean body mass, resting energy
expenditure is also reduced [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/6\">",
" 6",
" </a>",
" ]. Short stature is usually present during childhood and most patients fail to
have a pubertal growth spurt. Most patients with PWS have growth hormone
deficiency. (See",
" <a class=\"local\" href=\"#H13\">",
" 'Growth hormone deficiency'",
" </a>",
" below.)",
" </p>",
" <p class=\"headingAnchor\" id=\"H6\">",
" <span class=\"h2\">",
" Late childhood and adolescence",
" </span>",
" &nbsp;&mdash;&nbsp;Pubic and axillary hair may arise prematurely in children
with PWS due to adrenarche, but other secondary sexual characteristics generally
are delayed or incomplete. Testicular descent has occurred as late as adolescence.
Menarche is often delayed, perhaps in part because of concurrent obesity: menarche
may occur as late as age 30 years in response to significant weight loss [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/7\">",
" 7",
" </a>",
" ]. Other complications of obesity (eg, sleep apnea, cor pulmonale, diabetes
mellitus, and atherosclerosis), hypogonadism (osteoporosis), and behavioral issues
are common problems in adolescents and adults with PWS. Up to 25 percent of
patients with PWS have epilepsy, which is usually focal (eg, staring spells) [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/8\">",
" 8",
" </a>",
" ]. Scoliosis is frequently seen among patients with Prader-Willi syndrome,
with reported prevalence of 37 percent; 13 percent of patients require brace
treatment or surgery [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/9\">",
" 9",
" </a>",
" ]. (See",
" <a class=\"local\" href=\"#H11\">",
" 'Evaluation and management of comorbidities'",
" </a>",
" below.)",
" </p>",
" <p class=\"headingAnchor\" id=\"H76546868\">",
" <span class=\"h2\">",
" Adulthood",
" </span>",
" &nbsp;&mdash;&nbsp;In the past, survival after age 50 for individuals with PWS
was uncommon; many of the deaths in adults are attributable to obesity and its
complications, including cardiovascular problems, diabetes mellitus, and sleep
apnea [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/10\">",
" 10",
" </a>",
" ]. Advances in the care of these patients have improved life expectancy
somewhat. One case series describes 12 individuals older than 50 years of age [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/11\">",
" 11",
" </a>",
" ]. Most of these individuals had experienced decline in physical and
psychological function with advancing age. &nbsp;",
" </p>",
" <p class=\"headingAnchor\" id=\"H7\">",
" <span class=\"h1\">",
" BEHAVIOR CHARACTERISTICS",
" </span>",
" &nbsp;&mdash;&nbsp;Behavioral problems and learning difficulties are commonly
seen in Prader-Willi syndrome (PWS). Young children manifest temper tantrums,
stubbornness, and obsessive-compulsive behaviors that can impede school
performance. Some of these behaviors are similar to those found in pervasive
developmental disorder (autism); in one study, autistic-like behaviors were found
in 19 percent of individuals with PWS [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/12\">",
" 12",
" </a>",
" ]. Other studies suggest that these behaviors are particularly common in PWS
caused by uniparental disomy. (See",
" <a class=\"local\" href=\"#H10\">",
" 'Genetic testing'",
" </a>",
" below.) [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/13\">",
" 13",
" </a>",
" ]. Skin-picking behavior is common, as is rectal gouging [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/14,15\">",
" 14,15",
" </a>",
" ]. A variety of psychiatric symptoms and disorders have been reported among
adults including mood disorders and florid psychotic states [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/16\">",
" 16",
" </a>",
" ].",
" </p>",
" <p>",
" A mild to moderate degree of cognitive impairment is a commonly associated
characteristic; in one study the mean IQ of individuals with PWS was 40 points
below the population mean [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/17\">",
" 17",
" </a>",
" ]. The range of IQs is normally distributed, thus about 5 percent of
individuals with PWS will have IQs in the low-normal range (&gt;85), and 5 percent
will have severe intellectual disability (mental retardation) [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/18\">",
" 18",
" </a>",
" ].",
" </p>",
" <p>",
" Food-seeking behaviors may include eating garbage, eating frozen food, and
stealing resources to obtain food. Decreased ability to vomit and increased
tolerance of pain can promote binging on spoiled foods and delay treatment for
gastrointestinal disease. After episodes of binge eating (eg, at holidays), both
thin and obese individuals with PWS have developed abdominal discomfort with acute
gastric dilation seen on radiography [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/19\">",
" 19",
" </a>",
" ]. Choking episodes, typically associated with voracious eating habits, have
been reported as the cause of death among 8 percent of patients in one series of
sudden death cases [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/20\">",
" 20",
" </a>",
" ].",
" </p>",
" <p>",
" A variety of gastrointestinal peptides including pancreatic polypeptide,
cholecystokinin and ghrelin have been studied among individuals with PWS [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/21-23\">",
" 21-23",
" </a>",
" ]. The mechanism that causes impaired satiety in individuals with PWS is
unknown. However, levels of ghrelin, an orexigenic peptide, are persistently
elevated in individuals with PWS as compared to weight-matched controls, providing
a possible mechanism for the increased appetite in these patients [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/23,24\">",
" 23,24",
" </a>",
" ]. Because this does not appear to be the case for young lean patients with
PWS, some authors have proposed that a surge in ghrelin might precede the
hyperphagia and obesity observed in older children [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/25\">",
" 25",
" </a>",
" ]. To date, the role of ghrelin as a primary or secondary factor in the
satiety defect is unclear. Brain-derived neurotropic factor (BDNF) is another
potential mediator of hyperphagia in PWS; this neurohormone is decreased among
individuals with PWS [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/26\">",
" 26",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H8\">",
" <span class=\"h1\">",
" DIAGNOSIS",
" </span>",
" &nbsp;&mdash;&nbsp;The diagnosis of Prader-Willi syndrome (PWS) is suspected
in patients who have characteristic clinical features and is confirmed by genetic
testing. Clinical diagnostic criteria were developed in 1993 [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/27\">",
" 27",
" </a>",
" ]. For children three years of age or younger, the diagnosis of PWS is highly
likely if five points are scored from among these criteria (four from major
criteria). In children older than three years of age and adults, eight points are
required (five or more from among the major criteria).",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Major criteria (one point each): neonatal and infantile hypotonia, feeding
problems during infancy, excessive weight gain after infancy, characteristic facial
features, hypogonadism, global developmental delay or mild to moderate intellectual
disability, and hyperphagia.",
" </li>",
" <li>",
" Minor criteria (one half point each): decreased fetal movement,
characteristic behavior problems (usually multiple), sleep disturbance or sleep
apnea, short stature, hypopigmentation, small hands",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" feet, narrow hands with straight ulnar border, eye abnormalities (esotropia,
myopia), thick viscous saliva with crusting at corners of mouth, speech
articulation defects, and skin picking.",
" </li>",
" </ul>",
" </p>",
" <p>",
" However, now that definitive testing is available, it is appropriate to use
less rigid clinical criteria to determine who should undergo genetic testing.",
" </p>",
" <p class=\"headingAnchor\" id=\"H9\">",
" <span class=\"h2\">",
" Indications for genetic testing",
" </span>",
" &nbsp;&mdash;&nbsp;Based on a retrospective review of the clinical
characteristics of 90 patients with genetically confirmed PWS, molecular testing
should be considered in patients who have all of the following clinical features
for their age [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/28\">",
" 28",
" </a>",
" ]:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Birth to two years",
" <strong>",
" </strong>",
" </li>",
" </ul>",
" </p>",
" <p>",
" <ul class=\"hyphen-block\">",
" <li>",
" Hypotonia with poor suck",
" </li>",
" </ul>",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Two to six years",
" </li>",
" </ul>",
" </p>",
" <p>",
" <ul class=\"hyphen-block\">",
" <li>",
" Hypotonia with history of poor suck",
" </li>",
" <li>",
" Global developmental delay",
" </li>",
" </ul>",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" 6 to 12 years",
" </li>",
" </ul>",
" </p>",
" <p>",
" <ul class=\"hyphen-block\">",
" <li>",
" History of hypotonia with poor suck (hypotonia often persists)",
" </li>",
" <li>",
" Global developmental delay",
" </li>",
" <li>",
" Excessive eating (hyperphagia: obsession with food), with obesity if food
intake is uncontrolled",
" </li>",
" </ul>",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" 13 years through adulthood",
" </li>",
" </ul>",
" </p>",
" <p>",
" <ul class=\"hyphen-block\">",
" <li>",
" Cognitive impairment; usually mild mental retardation",
" </li>",
" <li>",
" Excessive eating (hyperphagia: obsession with food) with central obesity if
uncontrolled",
" </li>",
" <li>",
" Hypothalamic hypogonadism",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" typical behavior problems (including temper tantrums and obsessive-
compulsive features)",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H10\">",
" <span class=\"h2\">",
" Genetic testing",
" </span>",
" &nbsp;&mdash;&nbsp;Prader-Willi syndrome is caused by absence of expression of
the paternally active genes on the long arm of chromosome 15, either due to
deletions from the paternal chromosome, maternal disomy, or (rarely) defects in the
imprinting center. Molecular testing for PWS is highly sensitive, as standard
panels with a methylation analysis will detect more than 99 percent of cases [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/3\">",
" 3",
" </a>",
" ]. Testing is done in a sequence that allows identification of all potential
genetic defects (",
" <a class=\"graphic graphic_table graphicRef61992 \" href=\"UTD.htm?
32/16/33035\">",
" table 1",
" </a>",
" ) [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/28,29\">",
" 28,29",
" </a>",
" ]. A standard diagnostic panel for PWS begins with karyotype and methylation
studies, followed by fluorescence in-situ hybridization (FISH), and then
microsatellite probes to detect maternal uniparental disomy (UPD).",
" </p>",
" <p>",
" Further testing and genetic counseling may be necessary in families with a
child who has a mutation affecting the imprinting center or a parental chromosome
translocation. While these mutations are rare, they are associated with a risk of
recurrence in future pregnancies. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?16/8/16516?
source=see_link\">",
" \"Epidemiology and genetics of Prader-Willi syndrome\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H11\">",
" <span class=\"h1\">",
" EVALUATION AND MANAGEMENT OF COMORBIDITIES",
" </span>",
" &nbsp;&mdash;&nbsp;Additional diagnostic evaluation should be considered in
individuals with Prader-Willi syndrome (PWS) because of their increased risk for
hypogonadism and weight-related complications.",
" </p>",
" <p class=\"headingAnchor\" id=\"H12\">",
" <span class=\"h2\">",
" Hypothalamic and pituitary dysfunction",
" </span>",
" &nbsp;&mdash;&nbsp;Most patients exhibit evidence of hypothalamic and
pituitary dysfunction manifested as short stature, central obesity, hypogonadism,
and osteoporosis [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/30\">",
" 30",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H13\">",
" <span class=\"h3\">",
" Growth hormone deficiency",
" </span>",
" &nbsp;&mdash;&nbsp;Growth hormone secretion is generally blunted in PWS, and
the preponderance of evidence suggests that this is a primary abnormality of PWS,
rather than a consequence of obesity [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/30-33\">",
" 30-33",
" </a>",
" ]. If children with PWS have evidence of growth failure, they are likely to
have growth hormone deficiency. However, other causes of growth failure should be
excluded, including hypothyroidism and under-nutrition (if the child is young and
failing to thrive, or on a low-calorie diet).",
" </p>",
" <p>",
" Growth hormone has beneficial effects on body composition as well as linear
growth. However, patients with PWS and severe obesity or respiratory impairment may
be at increased risk for life-threatening adverse effects of growth hormone
treatment. (See",
" <a class=\"local\" href=\"#H26\">",
" 'Growth hormone treatment'",
" </a>",
" below.)",
" </p>",
" <p class=\"headingAnchor\" id=\"H14\">",
" <span class=\"h3\">",
" Hypogonadism",
" </span>",
" &nbsp;&mdash;&nbsp;Hypogonadism in PWS is characterized by low LH and inhibin
B and high FSH, features suggesting both hypothalamic and peripheral abnormalities
[",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/34\">",
" 34",
" </a>",
" ]. The vast majority of patients with PWS are sterile, but pregnancy has been
reported in at least two women [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/30\">",
" 30",
" </a>",
" ]. About two thirds of boys display cryptorchidism, for which surgery is
generally indicated. Treatment for hypogonadism may include administration of",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?32/25/33171?
source=see_link\">",
" human chorionic gonadotropin",
" </a>",
" or sex steroids, but protocols specific to PWS patients have not been
established [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/30,34\">",
" 30,34",
" </a>",
" ]. Until systematic studies of sex hormone replacement are reported, we
suggest that sex hormone therapy be offered, in consultation with an
endocrinologist if possible, if there are symptoms of hypogonadism, including lack
of secondary sexual development or decreased bone density. An expert panel has
suggested annual monitoring of sex steroids and bone mineral density in adolescents
and adults, with hormone replacement as indicated. Because of concerns about
hormonal effects on mood and behavior, replacement doses should be minimized and
titrated to the individual's response [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/35\">",
" 35",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H15\">",
" <span class=\"h3\">",
" Osteoporosis",
" </span>",
" &nbsp;&mdash;&nbsp;Serial dual energy x-ray absorptiometry (DXA) scans are
useful in monitoring bone density, as well as body composition. Low bone density
may prompt consideration of sex hormone replacement therapy",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" growth hormone treatment [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/30\">",
" 30",
" </a>",
" ]. Other causes of osteopenia should be excluded, including inadequate intake
of vitamin D and calcium, and hypothyroidism.",
" </p>",
" <p>",
" DXA scans should be obtained on all patients with PWS beginning at five years
of age, and every two to three years thereafter. In addition, calcium and vitamin D
intake should be monitored through periodic dietary recalls, and supplemented as
necessary to meet daily recommended intakes for both of these nutrients. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?6/38/6760?
source=see_link\">",
" \"Measurement of body composition in children\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H16\">",
" <span class=\"h3\">",
" Adrenal insufficiency",
" </span>",
" &nbsp;&mdash;&nbsp;A few reports have raised the possibility of central
adrenal insufficiency in patients with Prader-Willi syndrome; other investigations
have found normal cortisol response to testing [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/36-38\">",
" 36-38",
" </a>",
" ]. In a study of 25 patients, 60 percent had an abnormal response to a test of
ACTH secretory ability, suggesting that they might be at risk for acute adrenal
insufficiency under stress conditions [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/36\">",
" 36",
" </a>",
" ]. Whether the subclinical adrenal dysfunction detected by this laboratory
testing is responsible for some of the unexplained deaths observed in patients with
Prader-Willi syndrome remains to be determined. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?16/54/17255?
source=see_link&amp;anchor=H17#H17\">",
" \"Diagnosis of adrenal insufficiency in children\", section on 'Tests of ACTH
secretory ability'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H17\">",
" <span class=\"h3\">",
" Other neuroendocrine functions",
" </span>",
" &nbsp;&mdash;&nbsp;Thyroid hormones may be normal in PWS, but in our
experience up to 15 percent of patients have hypothyroidism. Thyroid and adrenal
status should be addressed in patients with PWS when clinically warranted.
Screening for hypothyroidism is appropriate in any child with growth failure or
decreased bone density, and those in whom there is an inadequate response to growth
hormone therapy.",
" </p>",
" <p class=\"headingAnchor\" id=\"H18\">",
" <span class=\"h2\">",
" Obesity-related problems",
" </span>",
" &nbsp;&mdash;&nbsp;Patients with PWS who develop obesity are at high risk for
all obesity-related medical problems. In addition to addressing the obesity itself,
providers should actively investigate for obesity-related comorbidities to minimize
morbidity and mortality. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/50/37674?
source=see_link\">",
" \"Comorbidities and complications of obesity in children and adolescents\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H19\">",
" <span class=\"h3\">",
" Type 2 diabetes",
" </span>",
" &nbsp;&mdash;&nbsp;Children and adolescents with PWS who have a BMI &gt;95",
" ^{",
" th",
"}",
" percentile should be screened for the development of type 2 diabetes by
measuring fasting blood glucose",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" performing oral glucose tolerance tests. The risk of glucose intolerance and
diabetes is increased if the patient is taking growth hormone, which can exacerbate
insulin resistance. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/50/37674?
source=see_link&amp;anchor=H5#H5\">",
" \"Comorbidities and complications of obesity in children and adolescents\",
section on 'Diabetes mellitus'",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?4/25/4506?
source=see_link\">",
" \"Epidemiology, presentation, and diagnosis of type 2 diabetes mellitus in
children and adolescents\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H20\">",
" <span class=\"h3\">",
" Sleep apnea",
" </span>",
" &nbsp;&mdash;&nbsp;Patients with PWS are at high risk for sleep related
disturbances including central apnea, obstructive apnea, and narcolepsy. Sleep-
disordered breathing occurs in at least 70 percent of children and young adults
with PWS [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/39\">",
" 39",
" </a>",
" ], and is associated with increased daytime sleepiness and behavioral
disturbances. Clinicians should monitor all patients for sleep-related symptoms,
including consistent snoring, pauses in breathing longer than five seconds, or
daytime sleepiness, particularly during intercurrent respiratory illnesses.
Patients with severe obesity or any clinical symptoms of sleep apnea should be
referred for a polysomnogram (sleep study) if possible and evaluated for
adenotonsillar hypertrophy. Tonsillectomy, adenoidectomy, or tracheostomy placement
may be required in patients with severe obstructive sleep apnea. CPAP treatment may
also be indicated, but is often not well tolerated by the patient. Patients with
substantial obstructive sleep apnea should be evaluated for cor pulmonale. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?43/38/44649?
source=see_link\">",
" \"Evaluation of suspected obstructive sleep apnea in children\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?39/17/40217?
source=see_link\">",
" \"Management of obstructive sleep apnea in children\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H21\">",
" <span class=\"h3\">",
" Other",
" </span>",
" &nbsp;&mdash;&nbsp;Other obesity-related problems frequently seen in obese
patients with PWS include dyslipidemia, cholelithiasis, gastroesophageal reflux,
non-alcoholic fatty liver disease, and hypertension. These are generally treated as
they would be in other patients with obesity. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/50/37674?
source=see_link\">",
" \"Comorbidities and complications of obesity in children and adolescents\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H22\">",
" <span class=\"h2\">",
" Additional risks",
" </span>",
" </p>",
" <p class=\"headingAnchor\" id=\"H23\">",
" <span class=\"h3\">",
" Gastric distension and rupture",
" </span>",
" &nbsp;&mdash;&nbsp;Several case reports and an autopsy study have described
acute gastric distension and necrosis in patients with PWS [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/40\">",
" 40",
" </a>",
" ]. The patient typically presents with progressive abdominal discomfort and
vomiting, in what may appear to be a flu-like syndrome. Patients may only complain
of mild abdominal discomfort despite significant gastric necrosis, consistent with
the high pain threshold often reported in patients with PWS. The disorder may or
may not be triggered by binge-eating episodes [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/19\">",
" 19",
" </a>",
" ]. Vomiting is often present in the syndrome of acute gastric distension,
whereas vomiting is uncommon in patients with PWS after episodes of binge eating.",
" </p>",
" <p class=\"headingAnchor\" id=\"H24\">",
" <span class=\"h3\">",
" Choking episodes",
" </span>",
" &nbsp;&mdash;&nbsp;Choking episodes attributed to oromotor uncoordination,
hypotonia, hyperphagia, voracious feeding habits, and decreased mastication were
reported by the families of 34 percent of patients who died suddenly [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/20\">",
" 20",
" </a>",
" ]. Choking was listed as a cause of death in 8 percent of patients. Training
in use of the Heimlich maneuver should be considered for all providers and families
of PWS patients.",
" </p>",
" <p class=\"headingAnchor\" id=\"H25\">",
" <span class=\"h3\">",
" Orthopedic problems",
" </span>",
" &nbsp;&mdash;&nbsp;Scoliosis is common in PWS. Scoliosis exceeding 10 percent
curvature affects up to 80 percent of patients, and 20 to 40 percent of patients
have clinically significant scoliosis [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/9,41\">",
" 9,41",
" </a>",
" ]. Approximately 30 percent of infants and children are affected, and the
prevalence increases with age [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/9,42\">",
" 9,42",
" </a>",
" ]. In patients with obesity, it may be difficult to detect scoliosis with a
physical examination, so radiographic evaluation is recommended.",
" </p>",
" <p>",
" Because the risk of scoliosis generally increases with height velocity, the
risk of scoliosis might be increased in patients treated with growth hormone (as
was shown for patients with Turner syndrome treated with growth hormone [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/43\">",
" 43",
" </a>",
" ]). However, studies have not confirmed that growth hormone therapy increases
the risk or severity of scoliosis in patients with PWS [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/44,45\">",
" 44,45",
" </a>",
" ].",
" </p>",
" <p>",
" Several case series have reported unusually high complication rates for
scoliosis surgery in individuals with PWS [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/46-48\">",
" 46-48",
" </a>",
" ]. The largest series described outcomes of scoliosis surgery among 16
patients with PWS [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/46\">",
" 46",
" </a>",
" ]. Nine of these patients experienced severe complications; four of which were
the development of severe progressive cervical-thoracic kyphosis above the fusion
requiring reoperation, and three of these were further complicated by spinal cord
injury.",
" </p>",
" <p>",
" Patients with PWS are also at increased risk for hip dysplasia and lower limb
alignment abnormalities. Unlike other children with obesity, they do not appear to
have increased risk for slipped capital femoral epiphysis [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/49\">",
" 49",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H26\">",
" <span class=\"h1\">",
" GROWTH HORMONE TREATMENT",
" </span>",
" &nbsp;&mdash;&nbsp;Children with Prader-Willi syndrome (PWS) and growth
failure are candidates for growth hormone treatment. Several clinical trials have
demonstrated beneficial effects of growth hormone treatment on linear growth [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/44,50-52\">",
" 44,50-52",
" </a>",
" ]. Body composition, including fat-free mass and bone density abnormalities,
also appears to improve with growth hormone treatment.",
" </p>",
" <p>",
" Use of growth hormone for children with growth failure and genetically
confirmed PWS was approved by the United States Food and Drug Administration (FDA)
in 2000, and has been approved for this use in most countries [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/53,54\">",
" 53,54",
" </a>",
" ]. Most individuals with PWS will have growth hormone deficiency when formally
tested. Nonetheless, it is generally not necessary to evaluate formally for growth
hormone deficiency before considering growth hormone treatment for patients with
PWS and growth failure. Growth failure is typically defined by the standards used
for children without PWS (decreased linear growth velocity or decreased height in
comparison to the mid-parental height prediction). Measurements of insulin-like
growth factor-1 (IGF-1) and insulin-like binding protein-3 (IGFBP-3) are used by
some endocrinologists for anecdotal evidence of growth hormone deficiency and are
sometimes used to target growth hormone doses.",
" </p>",
" <p>",
" There is increasing evidence that early initiation of growth hormone treatment
(eg, before two years of age) improves clinical outcomes, as detailed in the
following section. Early initiation of growth hormone could be difficult in the
United States, where the PWS indication requires growth failure [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/35\">",
" 35",
" </a>",
" ]. For infants and children with PWS who do not meet criteria for growth
failure, formal testing for growth hormone deficiency may assist the pediatric
endocrinologist and family in making decisions about early initiation of
treatment.",
" </p>",
" <p>",
" Because of reports of specific risks of growth hormone treatment for children
with PWS, warning labels have been added [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/55\">",
" 55",
" </a>",
" ]. Treatment of patients with somatostatin or",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?37/6/37991?
source=see_link\">",
" octreotide",
" </a>",
" has also been explored [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/56-58\">",
" 56-58",
" </a>",
" ], but has not been beneficial in patients with PWS. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?17/60/18376?
source=see_link\">",
" \"Diagnostic approach to short stature\"",
" </a>",
" and",
" <a class=\"local\" href=\"#H28\">",
" 'Safety'",
" </a>",
" below.)",
" </p>",
" <p class=\"headingAnchor\" id=\"H27\">",
" <span class=\"h2\">",
" Efficacy",
" </span>",
" &nbsp;&mdash;&nbsp;Many studies have investigated the effect of growth hormone
(GH) administration on linear growth, body composition and bone density in children
with PWS, and virtually all have demonstrated beneficial effects [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/44,50,59-66\">",
" 44,50,59-66",
" </a>",
" ]. The optimal age to begin treatment, dosing, and duration of therapy has not
been established.",
" </p>",
" <p>",
" The response to GH in children with PWS is greatest during the first 12 months
of therapy [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/44\">",
" 44",
" </a>",
" ]. Nevertheless, patients have had continued improvement in linear growth,
bone density, and body composition when GH has been administered in sufficient
doses for as long as five years [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/63\">",
" 63",
" </a>",
" ]. Even with long-term growth hormone treatment, body composition is not
completely normalized.",
" </p>",
" <p>",
" GH has generally been used in children with PWS older than the age of two
years. However, some studies have demonstrated beneficial effects in younger
children [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/64,65\">",
" 64,65",
" </a>",
" ]. In one report, administration of GH to children with PWS who were younger
than two years of age resulted in significantly increased lean body mass and
delayed fat tissue accumulation compared with a group that received coenzyme Q [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/64\">",
" 64",
" </a>",
" ]. Similar improvements in body composition with growth hormone therapy were
reported in a randomized, placebo-controlled trial of 29 infants and toddlers with
PWS (aged 4 to 37 months) [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/65\">",
" 65",
" </a>",
" ]. Initiating treatment before the age of 18 months was associated with
accelerated acquisition of mobility skills compared with controls of the same
age.",
" </p>",
" <p>",
" Additional long-term observation will be required to determine whether therapy
with GH increases adult height. The high cost of treatment with GH and the
possibility of side effects also are important issues for parents and clinicians to
consider.",
" </p>",
" <p>",
" We suggest that growth hormone treatment be offered to all patients with PWS
and growth failure, unless contraindicated by the presence of severe obesity (eg,
weight &gt;225 percent of ideal body weight), diabetes, respiratory compromise, or
severe sleep apnea. Starting doses of 1",
" <span class=\"nowrap\">",
" mg/m2/day",
" </span>",
" are appropriate for most patients (somewhat lower doses per kilogram in
patients that are significantly overweight), and the dose should be adjusted with
changes in body weight during the course of therapy. In addition, some providers
adjust dosing to achieve IGF-1 levels in the normal range to optimize linear growth
and minimize risks of adverse metabolic side effects. We continue treatment until
the epiphyses are closed.",
" </p>",
" <p>",
" Whether continuation of growth hormone treatment into adulthood provides
clinical benefit has not been established. However, there are modest benefits in
body composition and cognition when growth hormone is given to adults with PWS who
were not treated during childhood [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/67,68\">",
" 67,68",
" </a>",
" ]. These observations raise the possibility that continuation of GH treatment
after epiphyseal closure may also be beneficial, although this approach has not
been studied [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/35\">",
" 35",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?14/0/14345?
source=see_link&amp;anchor=H6#H6\">",
" \"Treatment of growth hormone deficiency in children\", section on 'Dosing
and monitoring'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H28\">",
" <span class=\"h2\">",
" Safety",
" </span>",
" &nbsp;&mdash;&nbsp;As of 2003, there were reports of at least seven fatalities
worldwide coinciding with the use of exogenous growth hormone treatment in children
with PWS [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/69\">",
" 69",
" </a>",
" ]. The deaths were associated with respiratory problems",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" were unexpected, and most occurred within the first three months of growth
hormone treatment. The patients had one or more of the following risk factors:
severe obesity, sleep apnea, or respiratory infection.",
" </p>",
" <p>",
" Whether the deaths were directly related to the use of growth hormone therapy
is unknown, since children with PWS have an increased risk of sudden unexpected
death independent of treatment with growth hormone [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/70,71\">",
" 70,71",
" </a>",
" ].",
" </p>",
" <p>",
" Growth hormone is postulated to have mixed effects on sleep-disordered
breathing:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Growth hormone therapy may worsen obstructive apnea by stimulating
adenotonsillar hypertrophy via IGF-1 signaling. This mechanism is supported by case
reports that correlate worsening obstructive apnea in some patients with higher
IGF-1 levels [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/72\">",
" 72",
" </a>",
" ].",
" </li>",
" <li>",
" Conversely, central hypoventilation may improve because of direct effects of
growth hormone on hypothalamic function. This mechanism is consistent with
observations that, in the majority of patients with PWS, growth hormone improves
sleep-disordered breathing",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" pulmonary function [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/72-74\">",
" 72-74",
" </a>",
" ].",
" </li>",
" </ul>",
" </p>",
" <p>",
" The increased short-term risks for obstructive sleep apnea during treatment
with GH tend to occur in patients with baseline obstructive symptoms or
intercurrent upper respiratory tract infections. As an example, in a study of young
patients with PWS (under 21 months of age), there was an increased frequency of
obstructive events associated with upper respiratory tract infections or
gastroesophageal reflux [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/75\">",
" 75",
" </a>",
" ]. In contrast, there were no changes in sleep-disordered breathing
attributable to growth hormone treatment.",
" </p>",
" <p>",
" Because of these concerns, the FDA has added labeling to growth hormone
products stating that GH therapy is contraindicated in patients with Prader-Willi
syndrome who are severely obese or have severe respiratory impairment [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/53,54,76\">",
" 53,54,76",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H29\">",
" <span class=\"h2\">",
" Pretreatment evaluation",
" </span>",
" &nbsp;&mdash;&nbsp;Patients with Prader-Willi syndrome should not begin growth
hormone therapy if they are severely obese (eg, &gt;225 percent of ideal body
weight).",
" </p>",
" <p>",
" Patients should be evaluated for upper airway obstruction or apnea before
starting growth hormone treatment and GH treatment should be interrupted if
patients develop signs of upper respiratory obstruction (including onset of or
increased snoring)",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" new onset of sleep apnea. In addition, patients should be monitored for
adverse progression of glucose tolerance and scoliosis [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/53-55,76-78\">",
" 53-55,76-78",
" </a>",
" ].",
" </p>",
" <p>",
" We suggest that all patients with PWS undergo polysomnography prior to
beginning growth hormone treatment. Growth hormone treatment should not proceed
until the sleep disordered breathing is effectively treated. Those with abnormal
polysomnograms should have follow up studies approximately one month after
beginning GH treatment, and all patients with PWS on GH treatment should be
clinically reevaluated if they develop intercurrent upper respiratory tract
infections or increased obstructive symptoms. Particular care should be taken in
managing this issue in infants and toddlers, who appear to be at the highest risk
for respiratory compromise because of underlying hypotonia. For these children, we
suggest monitoring oxygen saturation during sleep for the first one to two months
after starting GH treatment, if possible.",
" </p>",
" <p class=\"headingAnchor\" id=\"H30\">",
" <span class=\"h1\">",
" MANAGEMENT OF FEEDING AND OBESITY",
" </span>",
" </p>",
" <p class=\"headingAnchor\" id=\"H31\">",
" <span class=\"h2\">",
" Neonates and infants",
" </span>",
" &nbsp;&mdash;&nbsp;Patients with Prader-Willi syndrome (PWS) frequently
require medical care for a variety of issues, beginning initially with assistance
with management of hypotonia and poor feeding. Oromotor evaluation, swallow study,
and thickened high-calorie feedings are commonly used early in life; patients with
significant reflux or swallowing dysfunction may require gastrostomy or
fundoplication. The latter should be considered with caution given these
individuals' tendency to over-eat later in life. Caloric goals should be designed
to promote moderate rates of weight gain. Over-restriction prior to three years of
age (unless deemed medically necessary because of significant obesity) might limit
brain myelination and cognitive development, while excessively rapid growth may
increase the long-term predisposition to obesity. Growth standards (disease-
specific growth curves) have been developed for infants and toddlers with PWS [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/79\">",
" 79",
" </a>",
" ]. The standards were developed using a sample of 186 white infants with PWS
who were living in the United States and not treated with growth hormone. &nbsp;",
" </p>",
" <p>",
" Other interventions are offered to optimize cognitive and physical
development. Intensive physical and occupational therapies can assist with muscle
tone and strength. Speech therapy may assist with development of swallowing,
communication, and enunciation.",
" </p>",
" <p class=\"headingAnchor\" id=\"H32\">",
" <span class=\"h2\">",
" Older children and adults",
" </span>",
" &nbsp;&mdash;&nbsp;Controlling obesity through strict limitation of food
intake is the cornerstone of effective management of PWS. To achieve and maintain a
healthy body weight, caloric goals must often be set well below those predicted for
children without PWS. With these low-calorie diets, vitamin and mineral (calcium)
supplementation is usually required to meet daily requirements.",
" </p>",
" <p>",
" Some behavioral modification techniques have been helpful in engaging the
cooperation of the patient. However, strict limitation of access to food using
physical barriers (locks) and close supervision is generally necessary.
Coordination of efforts between the patient's family, school, and a
multidisciplinary care team is valuable. Stealing and hoarding food are common
behaviors, even when the individual is otherwise well behaved. For some patients, a
specialized highly structured group home environment is used to manage PWS-
associated obesity.",
" </p>",
" <p>",
" In spite of concerted efforts by the families and caregivers, many children
and adults with PWS will continue to have severe obesity and associated medical
problems. More invasive approaches to treatment of PWS-associated obesity have been
attempted, but the current literature provides minimal evidence on which to
evaluate the safety or efficacy of these approaches.",
" </p>",
" <p class=\"headingAnchor\" id=\"H33\">",
" <span class=\"h3\">",
" Pharmacotherapy",
" </span>",
" &nbsp;&mdash;&nbsp;Treatment with anorectic agents such as",
" <a class=\"drug drug_general\" href=\"UTD.htm?25/32/26118?source=see_link\">",
" phentermine",
" </a>",
" and fenfluramine has not been effective in controlling appetite in patients
with PWS. Selective serotonin reuptake inhibitors (SSRIs) may be effective for many
of the behavioral symptoms in patients with PWS, but there is little evidence that
these drugs have specific effects on binge eating or weight gain [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/14\">",
" 14",
" </a>",
" ]. Similarly,",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?20/60/21448?
source=see_link\">",
" topiramate",
" </a>",
" did not decrease appetite, food intake, or weight status of adults with PWS in
a brief open-label trial, although it may decrease self-injurious behaviors [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/80\">",
" 80",
" </a>",
" ]. Other classes of psychotropic drugs including neuroleptics may be useful in
treatment of behavioral symptoms, but their benefits must be weighed against their
potential weight-promoting side effects [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/14,80\">",
" 14,80",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H34\">",
" <span class=\"h3\">",
" Surgical weight loss procedures",
" </span>",
" &nbsp;&mdash;&nbsp;There are scattered reports of surgical weight loss
procedures in patients with PWS, including gastric bypass, biliopancreatic
diversion, and gastric restrictive procedures. The literature in this area consists
of case reports, most with follow-up of less than two years, and results are
inconsistent [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/81,82\">",
" 81,82",
" </a>",
" ]. Some of the reports are more than 20 years old, and describe surgical
techniques that are no longer used. However, it appears that there may be fewer
benefits and greater risks of weight loss surgery for individuals with PWS as
compared to other individuals with obesity.",
" </p>",
" <p>",
" In a retrospective review of PWS patients undergoing weight loss surgery, 63
percent of those undergoing gastric bypass had poor weight loss [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/83\">",
" 83",
" </a>",
" ]. There may be some long-term efficacy for the most malabsorptive of these
procedures (biliopancreatic diversion) [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/81\">",
" 81",
" </a>",
" ], but these operations also confer increased risks because of chronic
malabsorption of micronutrients and electrolytes. Patients with PWS may be at
particularly high risk after operations causing malabsorption because they already
have an increased risk for osteoporosis [",
" <a class=\"abstract\" href=\"UTD.htm?0/8/134/abstract/83\">",
" 83",
" </a>",
" ]. (See",
" <a class=\"local\" href=\"#H15\">",
" 'Osteoporosis'",
" </a>",
" above.) Furthermore, surgical procedures that restrict the stomach may be
particularly risky for patients with PWS, as there are reports of gastric dilation
and necrosis after gastric restrictive procedures.",
" </p>",
" <p>",
" Until more is known about the long-term efficacy and safety of surgical
interventions in patients with PWS, these procedures cannot be generally
recommended.",
" </p>",
" <p class=\"headingAnchor\" id=\"H35\">",
" <span class=\"h1\">",
" SUMMARY AND RECOMMENDATIONS",
" </span>",
" &nbsp;&mdash;&nbsp;Prader-Willi syndrome (PWS) is the most common syndromic
form of obesity, but is still rare in comparison to non-syndromic obesity.",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Prominent clinical features in infants and toddlers are hypotonia and
feeding problems, sometimes leading to failure to thrive. Hypotonic infants with
PWS are also at risk for asphyxia. (See",
" <a class=\"local\" href=\"#H2\">",
" 'Clinical manifestations'",
" </a>",
" above.)",
" </li>",
" <li>",
" Common clinical features in older children, adolescents, and adults are
voracious appetite, with obesity if food is not restricted, decreased cognition,
and hypogonadism. Short stature relative to genetic background usually becomes
apparent during childhood or puberty. (See",
" <a class=\"local\" href=\"#H2\">",
" 'Clinical manifestations'",
" </a>",
" above.)",
" </li>",
" <li>",
" Genetic testing for PWS is highly sensitive (&gt;99 percent sensitivity)
using disease-specific test panels, and is the gold standard for making the
diagnosis of PWS. Clinical screening is designed to determine which patients should
have genetic testing. (See",
" <a class=\"local\" href=\"#H9\">",
" 'Indications for genetic testing'",
" </a>",
" above and",
" <a class=\"local\" href=\"#H10\">",
" 'Genetic testing'",
" </a>",
" above.)",
" </li>",
" <li>",
" Care of the patient with PWS includes monitoring and management of comorbid
conditions. Important comorbidities that can be acutely life-threatening include
sleep apnea, diabetes mellitus, and gastric distension and rupture. Other comorbid
conditions associated with obesity are common. (See",
" <a class=\"local\" href=\"#H11\">",
" 'Evaluation and management of comorbidities'",
" </a>",
" above.)",
" </li>",
" <li>",
" Unless contraindicated, we suggest treatment with growth hormone in all
children and adolescents with PWS who have clinical evidence of growth failure (",
" <a class=\"grade\" href=\"._grade_5?title=Grade 2B\">",
" Grade 2B",
" </a>",
" ). Growth hormone therapy improves linear growth and also body composition,
including fat-free mass and bone density abnormalities. Contraindications include
severe obesity, severe sleep apnea, or respiratory compromise, as there may be an
increased risk of death in these patients. Patients should be closely monitored for
the development of respiratory obstruction, particularly during the first few
months of growth hormone treatment. (See",
" <a class=\"local\" href=\"#H26\">",
" 'Growth hormone treatment'",
" </a>",
" above.)",
" </li>",
" <li>",
" The optimal duration of growth hormone treatment has not been established.
The most rapid improvements are seen during the first 12 months of therapy, and
more modest improvements are seen for up to five years of treatment if sufficient
doses of growth hormone are given. (See",
" <a class=\"local\" href=\"#H26\">",
" 'Growth hormone treatment'",
" </a>",
" above.)",
" </li>",
" <li>",
" Management of feeding and obesity is a critical part of care for patients
with PWS. We recommend designing a highly structured living environment in which
access to food is strictly limited through close supervision and physical barriers
(",
" <a class=\"grade\" href=\"._grade_2?title=Grade 1B\">",
" Grade 1B",
" </a>",
" ). (See",
" <a class=\"local\" href=\"#H30\">",
" 'Management of feeding and obesity'",
" </a>",
" above.)",
" </li>",
" <li>",
" No pharmacological agent, including",
" <a class=\"drug drug_general\" href=\"UTD.htm?25/32/26118?
source=see_link\">",
" phentermine",
" </a>",
" ,",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?20/60/21448?
source=see_link\">",
" topiramate",
" </a>",
" , or SSRIs, has been shown to be helpful in controlling appetite or binge
eating and we suggest NOT using these agents for this purpose (",
" <a class=\"grade\" href=\"._grade_6?title=Grade 2C\">",
" Grade 2C",
" </a>",
" ). Psychotropic drugs are often used for behavior control. (See",
" <a class=\"local\" href=\"#H33\">",
" 'Pharmacotherapy'",
" </a>",
" above.)",
" </li>",
" <li>",
" Weight loss surgery for patients with PWS has been reported, but not well
studied. There are concerns about both efficacy and safety of the procedure in
these patients. Until better information is available, we suggest NOT performing
weight loss surgery for patients with PWS unless it is in the context of a disease-
specific research protocol (",
" <a class=\"grade\" href=\"._grade_6?title=Grade 2C\">",
" Grade 2C",
" </a>",
" ). (See",
" <a class=\"local\" href=\"#H34\">",
" 'Surgical weight loss procedures'",
" </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>",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/134/abstract/45\">",
" Nagai T, Obata K, Ogata T, et al. Growth hormone therapy and scoliosis in
patients with Prader-Willi syndrome. Am J Med Genet A 2006; 140:1623.",
" </a>",
" </li>",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/134/abstract/46\">",
" Accadbled F, Odent T, Moine A, et al. Complications of scoliosis surgery in
Prader-Willi syndrome. Spine (Phila Pa 1976) 2008; 33:394.",
" </a>",
" </li>",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/134/abstract/47\">",
" Rees D, Jones MW, Owen R, Dorgan JC. Scoliosis surgery in the Prader-Willi
syndrome. J Bone Joint Surg Br 1989; 71:685.",
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" Tokutomi T, Chida A, Asano Y, et al. A non-obese boy with Prader-Willi
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" Kroonen LT, Herman M, Pizzutillo PD, Macewen GD. Prader-Willi Syndrome:
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" Davies PS, Evans S, Broomhead S, et al. Effect of growth hormone on height,
weight, and body composition in Prader-Willi syndrome. Arch Dis Child 1998;
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" Angulo MA, Castro-Magana M, Lamerson M, et al. Final adult height in
children with Prader-Willi syndrome with and without human growth hormone
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" Sipil&auml; I, Sintonen H, Hietanen H, et al. Long-term effects of growth
hormone therapy on patients with Prader-Willi syndrome. Acta Paediatr 2010;
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" Humatrope&reg; Somatropin (rDNA origin) for injection vials and cartridges
for use with the HumatroPen&trade; injection device. Eli Lilly and Company,
Indianapolis, March 2004.",
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" Nutropin Depot&reg; [somatropin (rDNA origin) for injectable suspension].
Genentech, Inc. San Francisco, October 2004.",
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growth hormone in children: the Lawson Wilkins Pediatric Endocrinology Society Drug
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" Haqq AM, Stadler DD, Rosenfeld RG, et al. Circulating ghrelin levels are
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" Tan TM, Vanderpump M, Khoo B, et al. Somatostatin infusion lowers plasma
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" De Waele K, Ishkanian SL, Bogarin R, et al. Long-acting octreotide treatment
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" Obata K, Sakazume S, Yoshino A, et al. Effects of 5 years growth hormone
treatment in patients with Prader-Willi syndrome. J Pediatr Endocrinol Metab 2003;
16:155.",
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" Eiholzer U, L'allemand D, Schlumpf M, et al. Growth hormone and body
composition in children younger than 2 years with Prader-Willi syndrome. J Pediatr
2004; 144:753.",
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" Carrel AL, Moerchen V, Myers SE, et al. Growth hormone improves mobility and
body composition in infants and toddlers with Prader-Willi syndrome. J Pediatr
2004; 145:744.",
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" Galassetti P, Saetrum Opgaard O, Cassidy SB, Pontello A. Nutrient intake and
body composition variables in Prader-Willi syndrome--effect of growth hormone
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" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/134/abstract/67\">",
" Mogul HR, Lee PD, Whitman BY, et al. Growth hormone treatment of adults with
Prader-Willi syndrome and growth hormone deficiency improves lean body mass,
fractional body fat, and serum triiodothyronine without glucose impairment: results
from the United States multicenter trial. J Clin Endocrinol Metab 2008; 93:1238.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/134/abstract/68\">",
" Gondoni LA, Vismara L, Marzullo P, et al. Growth hormone therapy improves
exercise capacity in adult patients with Prader-Willi syndrome. J Endocrinol Invest
2008; 31:765.",
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[rDNA origin]) for injection). Available at
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" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/134/abstract/70\">",
" Nagai T, Obata K, Tonoki H, et al. Cause of sudden, unexpected death of
Prader-Willi syndrome patients with or without growth hormone treatment. Am J Med
Genet A 2005; 136:45.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/134/abstract/71\">",
" Schrander-Stumpel CT, Curfs LM, Sastrowijoto P, et al. Prader-Willi
syndrome: causes of death in an international series of 27 cases. Am J Med Genet A
2004; 124A:333.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/134/abstract/72\">",
" Miller J, Silverstein J, Shuster J, et al. Short-term effects of growth
hormone on sleep abnormalities in Prader-Willi syndrome. J Clin Endocrinol Metab
2006; 91:413.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/134/abstract/73\">",
" Haqq AM, Stadler DD, Jackson RH, et al. Effects of growth hormone on
pulmonary function, sleep quality, behavior, cognition, growth velocity, body
composition, and resting energy expenditure in Prader-Willi syndrome. J Clin
Endocrinol Metab 2003; 88:2206.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/134/abstract/74\">",
" Festen DA, de Weerd AW, van den Bossche RA, et al. Sleep-related breathing
disorders in prepubertal children with Prader-Willi syndrome and effects of growth
hormone treatment. J Clin Endocrinol Metab 2006; 91:4911.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/134/abstract/75\">",
" Miller JL, Shuster J, Theriaque D, et al. Sleep disordered breathing in
infants with Prader-Willi syndrome during the first 6 weeks of growth hormone
therapy: a pilot study. J Clin Sleep Med 2009; 5:448.",
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Evaluation and Research (CDER) -- September 2004. Available at
www.fda.gov/medwatch/SAFETY/2004/sep04.htm (Accessed on January 18, 2006).",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/134/abstract/77\">",
" Craig ME, Cowell CT, Larsson P, et al. Growth hormone treatment and adverse
events in Prader-Willi syndrome: data from KIGS (the Pfizer International Growth
Database). Clin Endocrinol (Oxf) 2006; 65:178.",
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" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/134/abstract/78\">",
" Lindgren AC. Somatropin therapy for children with prader-willi syndrome :
guidelines for use. Treat Endocrinol 2006; 5:223.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/134/abstract/79\">",
" Butler MG, Sturich J, Lee J, et al. Growth standards of infants with Prader-
Willi syndrome. Pediatrics 2011; 127:687.",
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" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/134/abstract/80\">",
" Shapira NA, Lessig MC, Lewis MH, et al. Effects of topiramate in adults with
Prader-Willi syndrome. Am J Ment Retard 2004; 109:301.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/134/abstract/81\">",
" Marinari GM, Camerini G, Novelli GB, et al. Outcome of biliopancreatic
diversion in subjects with Prader-Willi Syndrome. Obes Surg 2001; 11:491.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/134/abstract/82\">",
" Grugni G, Guzzaloni G, Morabito F. Failure of biliopancreatic diversion in
Prader-Willi syndrome. Obes Surg 2000; 10:179.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/8/134/abstract/83\">",
" Scheimann AO, Butler MG, Gourash L, et al. Critical analysis of bariatric
procedures in Prader-Willi syndrome. J Pediatr Gastroenterol Nutr 2008; 46:80.",
" </a>",
" </li>",
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" SUMMARY &amp; RECOMMENDATIONS",
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" INTRODUCTION",
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" CLINICAL MANIFESTATIONS",
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" Prenatal",
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" Infancy",
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" Early childhood",
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" Adulthood",
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" BEHAVIOR CHARACTERISTICS",
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" DIAGNOSIS",
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" Indications for genetic testing",
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" Genetic testing",
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" </li>",
" <li class=\"plainItem\">",
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" EVALUATION AND MANAGEMENT OF COMORBIDITIES",
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" Hypothalamic and pituitary dysfunction",
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" - Growth hormone deficiency",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H14\">",
" - Hypogonadism",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H15\">",
" - Osteoporosis",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H16\">",
" - Adrenal insufficiency",
" </a>",
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" - Other neuroendocrine functions",
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" Obesity-related problems",
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" - Type 2 diabetes",
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" - Sleep apnea",
" </a>",
" </li>",
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" - Other",
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" Additional risks",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H23\">",
" - Gastric distension and rupture",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H24\">",
" - Choking episodes",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H25\">",
" - Orthopedic problems",
" </a>",
" </li>",
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" <a class=\"outlineLink\" href=\"#H26\">",
" GROWTH HORMONE TREATMENT",
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" <a class=\"outlineLink\" href=\"#H27\">",
" Efficacy",
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" Safety",
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" Pretreatment evaluation",
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" MANAGEMENT OF FEEDING AND OBESITY",
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" Neonates and infants",
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" Older children and adults",
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" - Pharmacotherapy",
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" - Surgical weight loss procedures",
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" </li>",
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" <a class=\"outlineLink\" href=\"#H35\">",
" SUMMARY AND RECOMMENDATIONS",
" </a>",
" </li>",
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" <a href=\"#references\">",
" REFERENCES",
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" Genetic test panel for PWS",
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" <h1>",
" RELATED TOPICS",
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" <ul>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/50/37674?
source=related_link\">",
" Comorbidities and complications of obesity in children and adolescents",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?16/54/17255?
source=related_link\">",
" Diagnosis of adrenal insufficiency in children",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?17/60/18376?
source=related_link\">",
" Diagnostic approach to short stature",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?16/8/16516?
source=related_link\">",
" Epidemiology and genetics of Prader-Willi syndrome",
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source=related_link\">",
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" Management of obstructive sleep apnea in children",
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" </li>",
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source=related_link\">",
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source=related_link\">",
" Treatment of growth hormone deficiency in children",
" </a>",
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" </div>",
" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Reproduced with permission from: Drs. Ashfaq Marghoob and Natalia Jaimes.",
" </div>",
" </div>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 616px\">",
" <div class=\"ttl\">",
" Dermoscopic structures seen in melanocytic lesions and their histopathological
correlations",
" </div>",
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" </div>",
" <div class=\"lgnd\">",
" List continued in figure \"Dermoscopic structures 2\". Melanocytic neoplasms:
Dermoscopic structures and histopathologic correlation.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Reference:",
" <br/>",
" <ol>",
" <li>",
" Jaimes N, Braun RP, Stolz W, et al. White globules correlate with balloon
cell nevi nests. J Am Acad Dermatol 2011; 65:e119.",
" </li>",
" </ol>",
" <br/>",
" Reproduced with permission from: Drs. Ashfaq Marghoob and Natalia Jaimes.",
" </div>",
" </div>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 616px\">",
" <div class=\"ttl\">",
" Dermoscopic structures seen in melanocytic lesions and their histopathologic
correlations, continued",
" ^{",
" [1-3]",
"}",
" </div>",
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" </div>",
" <div class=\"lgnd\">",
" This is a continuation of figure \"Dermoscopic structures 1\". Melanocytic
neoplasms: Dermoscopic structures and histopathologic correlation.",
" <div class=\"footnotes\">",
" * Shiny white structures can also be seen in non-melanocytic lesions.
Chrysalis/crystalline structures (also known as white shiny streaks) in melanocytic
lesions are most common in melanoma and Spitz nevi",
" ^{",
" [8]",
"}",
" . Both chrysalis/crystalline structures and white shiny areas are common in
dermatofibromas and basal cell carcinomas",
" ^{",
" [9,10]",
"}",
" . Rosettes are more common in actinic keratosis and squamous cell
carcinomas",
" ^{",
" [5]",
"}",
" .",
" </div>",
" <div class=\"reference\">",
" References:",
" <br>",
" <ol>",
" <li>",
" Pehamberger H, Steiner A, Wolff K. In vivo epiluminescence microscopy of
pigmented skin lesions. I. Pattern analysis of pigmented skin lesions. J Am Acad
Dermatol 1987; 17:571.",
" </li>",
" <li>",
" Argenziano G, Soyer HP, Chimenti S, et al. Dermoscopy of pigmented skin
lesions: results of a consensus meeting via the Internet. J Am Acad Dermatol 2003;
48:679.",
" </li>",
" <li>",
" Braun RP, Rabinovitz HS, Oliviero M, et al. Dermoscopy of pigmented skin
lesions. J Am Acad Dermatol 2005; 52:109.",
" </li>",
" <li>",
" Zalaudek I, Argenziano G, Ferrara G, et al. Clinically equivocal
melanocytic skin lesions with features of regression: a dermoscopic-pathological
study. Br J Dermatol 2004; 150:64.",
" </li>",
" <li>",
" Liebman TN, Rabinovitz HS, Balagula Y, et al. White Shiny Structures in
Melanoma and BCC. Arch Dermatol 2012; 148:146",
" </li>",
" <li>",
" Cuellar F, Vilalta A, Puig S, et al. New dermoscopic pattern in actinic
keratosis and related conditions. Arch Dermatol 2009; 145:732.",
" </li>",
" <li>",
" Balagula Y, Braun RP, Rabinovitz HS, et al. The significance of
crystalline/chrysalis structures in the diagnosis of melanocytic and nonmelanocytic
lesions. J Am Acad Dermatol 2011. Epub ahead of print.",
" </li>",
" <li>",
" Di Stefani A, Campbell TM, Malvehy J, et al. Shiny white streaks: An
additional dermoscopic finding in melanomas viewed using contact polarised
dermoscopy. Australas J Dermatol 2010; 51:295.",
" </li>",
" <li>",
" Marghoob AA, Cowell L, Kopf AW, Scope A. Observation of chrysalis
structures with polarized dermoscopy. Arch Dermatol 2009; 145:618.",
" </li>",
" <li>",
" Altamura D, Menzies SW, Argenziano G, et al. Dermatoscopy of basal cell
carcinoma: morphologic variability of global and local features and accuracy of
diagnosis. J Am Acad Dermatol 2010; 62:67.",
" </li>",
" </ol>",
" Reproduced with permission from: Drs. Ashfaq Marghoob and Natalia Jaimes.",
" </br>",
" </div>",
" </div>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 616px\">",
" <div class=\"ttl\">",
" Non-melanocytic lesions: Dermoscopic structures and histopathological
correlation",
" ^{",
" [1-4]",
"}",
" </div>",
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" </div>",
" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" References:",
" <br>",
" <ol>",
" <li>",
" Argenziano G, Soyer HP, Chimenti S, et al. Dermoscopy of pigmented skin
lesions: results of a consensus meeting via the Internet. J Am Acad Dermatol 2003;
48:679.",
" </li>",
" <li>",
" Braun RP, Rabinovitz HS, Oliviero M, et al. Dermoscopy of pigmented skin
lesions. J Am Acad Dermatol 2005; 52:109.",
" </li>",
" <li>",
" Braun RP, Rabinovitz HS, Krischer J, et al. Dermoscopy of pigmented
seborrheic keratosis: a morphological study. Arch Dermatol 2002; 138:1556.",
" </li>",
" <li>",
" Scope A, Benvenuto-Andrade C, Agero AL, Marghoob AA. Nonmelanocytic
lesions defying the two-step dermoscopy algorithm. Dermatol Surg 2006; 32:1398.",
" </li>",
" <li>",
" Stricklin SM, Stoacker WV, Oliviero MC, et al. Cloudy and starry milia-
like cysts: how well do they distinguish seborrheic keratoses from malignant
melanomas? JEADV 2011.",
" </li>",
" </ol>",
" <br>",
" Reproduced with permission from: Drs. Ashfaq Marghoob and Natalia Jaimes.",
" </br>",
" </br>",
" </div>",
" </div>",
" </div>",
" </div>",
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" <div class=\"figure\">",
" <div class=\"ttl\">",
" The RODS&copy; mnemonic for difficult extraglottic airway placement",
" </div>",
" <div class=\"cntnt\">",
" <table cellspacing=\"0\">",
" <tr>",
" <td>",
" <strong>",
" R",
" </strong>",
" estricted mouth opening",
" </td>",
" </tr>",
" <tr>",
" <td>",
" <strong>",
" O",
" </strong>",
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" </td>",
" </tr>",
" <tr>",
" <td>",
" <strong>",
" D",
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" </td>",
" </tr>",
" <tr>",
" <td>",
" <strong>",
" S",
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" tiff lungs or cervical spine",
" </td>",
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" </div>",
" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" &copy; The Difficult Airway Course&reg;: Emergency.",
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var title_f0_8_137="GH evaluation cancer survivors";
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" &copy;2013 UpToDate",
" ^{",
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title=\"Print this page\"/>",
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" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
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" <div class=\"figure\">",
" <div class=\"ttl\">",
" Evaluation for growth hormone deficiency in childhood cancer survivors",
" </div>",
" <div class=\"cntnt\">",
" <table cellspacing=\"0\">",
" <tbody>",
" <tr>",
" <td class=\"subtitle1_left\" colspan=\"1\" rowspan=\"3\">",
" History",
" </td>",
" <td>",
" Cranial irradiation",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Total body radiation",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Chemotherapy",
" </td>",
" </tr>",
" <tr>",
" <td class=\"subtitle1_left\" colspan=\"1\" rowspan=\"3\">",
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" </td>",
" <td>",
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" </tr>",
" <tr>",
" <td>",
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" </td>",
" </tr>",
" <tr>",
" <td>",
" Truncal fat distribution",
" </td>",
" </tr>",
" <tr>",
" <td class=\"subtitle1_left\" colspan=\"1\" rowspan=\"3\">",
" Review of systems*",
" </td>",
" <td>",
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" </td>",
" </tr>",
" <tr>",
" <td>",
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" </td>",
" </tr>",
" <tr>",
" <td>",
" Hypoglycemia",
" </td>",
" </tr>",
" <tr>",
" <td class=\"subtitle1_left\" colspan=\"1\" rowspan=\"3\">",
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" </td>",
" <td>",
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" </td>",
" </tr>",
" <tr>",
" <td>",
" IGF BP3",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Bone maturation",
" </td>",
" </tr>",
" <tr>",
" <td class=\"subtitle1_left\">",
" Definitive tests",
" </td>",
" <td>",
" Stimulation test(s): arginine clonidine",
" </td>",
" </tr>",
" <tr>",
" <td class=\"subtitle1_left\" colspan=\"1\" rowspan=\"4\">",
" Associated endocrinopathies",
" </td>",
" <td>",
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" </td>",
" </tr>",
" <tr>",
" <td>",
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" <tr>",
" <td>",
" Precocious puberty",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Gonadotropin deficiency",
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" </tr>",
" </tbody>",
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" </div>",
" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" IGF-I: insulin-like growth factor-I; IGF BP3: insulin-like growth factor
binding protein 3; ACTH: adrenocorticotropin.",
" <br>",
" * Patients have often accommodated to their symptoms and do not complain.",
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" </div>",
" <div class=\"reference\">",
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" </div>",
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" </div>",
" <div class=\"cntnt\">",
" <table cellspacing=\"0\">",
" <tbody>",
" <tr>",
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" <tr>",
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" </td>",
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" </p>",
" </td>",
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" <tr>",
" <td class=\"indent1\">",
" Tabun",
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" </tr>",
" <tr>",
" <td class=\"indent1\">",
" Sarin",
" </td>",
" </tr>",
" <tr>",
" <td class=\"indent1\">",
" Soman",
" </td>",
" </tr>",
" <tr>",
" <td class=\"indent1\">",
" VX",
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" </tr>",
" <tr>",
" <td class=\"subtitle2_left\">",
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" </td>",
" <td rowspan=\"3\">",
" Airway edema, upper airway obstruction, bronchospasm",
" </td>",
" <td rowspan=\"3\">",
" <p>",
" Rapid identification of upper airway obstruction",
" </p>",
" <p>",
" Rapid identification of bronchospasm",
" </p>",
" </td>",
" </tr>",
" <tr>",
" <td class=\"indent1\">",
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" </tr>",
" <tr>",
" <td class=\"indent1\">",
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" </tr>",
" <tr>",
" <td class=\"subtitle2_left\">",
" Choking agents",
" </td>",
" <td rowspan=\"6\">",
" Rapid, progressive, non-cardiogenic pulmonary edema and acute lung injury,
bronchospasm, laryngospasm",
" </td>",
" <td rowspan=\"6\">",
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" Earliest indicator of respiratory compromise",
" </p>",
" <p>",
" Rapid identification of bronchospasm",
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" </td>",
" </tr>",
" <tr>",
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" </tr>",
" <tr>",
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" </tr>",
" <tr>",
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" <tr>",
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" <tr>",
" <td class=\"indent1\">",
" Ricin",
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" </tr>",
" <tr>",
" <td class=\"subtitle2_left\">",
" Cyanide",
" </td>",
" <td>",
" Sudden loss of consciousness/coma, seizures, metabolic acidosis with
tachypnea, apnea",
" </td>",
" <td>",
" <p>",
" Direct measure of ventilatory status",
" </p>",
" <p>",
" Accurate readings during seizure activity",
" </p>",
" <p>",
" Earliest indicator of respiratory compromise",
" </p>",
" <p>",
" Non-invasive identification of metabolic acidosis",
" </p>",
" </td>",
" </tr>",
" <tr>",
" <td class=\"subtitle2_left\">",
" Incapacitating agents",
" </td>",
" <td rowspan=\"3\">",
" Laryngospasm, bronchospasm, respiratory failure",
" </td>",
" <td rowspan=\"3\">",
" <p>",
" Rapid identification of laryngospasm",
" </p>",
" <p>",
" Rapid identification of bronchospasm",
" </p>",
" <p>",
" Earliest indicator of respiratory compromise",
" </p>",
" </td>",
" </tr>",
" <tr>",
" <td class=\"indent1\">",
" Lacrimators (Mace)",
" </td>",
" </tr>",
" <tr>",
" <td class=\"indent1\">",
" Capsaicin",
" </td>",
" </tr>",
" </tbody>",
" </table>",
" </div>",
" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Reproduced with permission from: Krauss B. Capnography as a rapid assessment
and triage tool for chemical terrorism.&nbsp;Pediatr Emerg Care 2005; 21:493.
Copyright &copy; 2005 Lippincott Williams &amp; Wilkins.",
" </div>",
" </div>",
" </div>",
" </div>",
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" </div>",
" <div class=\"lgnd\">",
" The effect of increasing sodium intake on the mean arterial pressure. In
normal animals, sodium intake can be raised from 1 to 25 meq/kg per day with
virtually no elevation in the systemic blood pressure. In this setting, sodium
excretion can be increased by lowering renin release without requiring a rise in
BP. If, however, angiotensin II and aldosterone are fixed at either low or high
levels, then there is a much lesser degree of tubular adaptation to increasing
sodium intake. As a result, there is initial sodium retention until the renal
perfusion pressure rises high enough to promote excretion of the excess sodium by
pressure natriuresis. Overt hypertension is seen with high angiotensin II levels.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Data from Guyton, AC, Science 1991; 252:1813.",
" </div>",
" </div>",
" </div>",
" </div>",
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\">",
" </div>",
" <div class=\"lgnd\">",
" The actions of the ankle include dorsiflexion, plantarflexion, eversion, and
inversion.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f0_8_140=[""].join("\n");
var outline_f0_8_140=null;
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var outline_f0_8_141=null;
var title_f0_8_142="Defect following nail unit excision";
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" </div>",
" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" </div>",
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" Courtesy of Phoebe Rich, MD.",
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" <a href=\"UTD.htm?6/42/6818\">",
" Patient information: Anesthesia (The Basics)",
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" <a href=\"UTD.htm?22/18/22820\">",
" Patient information: Abnormal uterine bleeding (Beyond the Basics)",
" </a>",
" </dd>",
" <dd>",
" <a href=\"UTD.htm?22/35/23094\">",
" Patient information: Menorrhagia (excessive menstrual bleeding) (Beyond
the Basics)",
" </a>",
" </dd>",
" <dd>",
" <a href=\"UTD.htm?20/20/20804\">",
" Patient information: Uterine fibroids (Beyond the Basics)",
" </a>",
" </dd>",
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" Patient information: Endometrial ablation (The Basics)",
" </div>",
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editors/patient-information\">",
" Written by the doctors and editors at UpToDate",
" </a>",
" <div id=\"topicText\">",
" <p class=\"headingAnchor\" id=\"H261992089\">",
" <span class=\"h1\">",
" What is endometrial ablation?",
" </span>",
" &nbsp;&mdash;&nbsp;Endometrial ablation (EA) is a surgery that makes a
woman&rsquo;s period much lighter or stops it completely. It works by scarring the
lining of the uterus (",
" <a class=\"graphic graphic_figure graphicRef80271 \" href=\"UTD.htm?
14/52/15171\">",
" figure 1",
" </a>",
" ).",
" </p>",
" <p class=\"headingAnchor\" id=\"H261992074\">",
" <span class=\"h1\">",
" Why might a woman get EA?",
" </span>",
" &nbsp;&mdash;&nbsp;Your doctor might recommend EA if you have heavy periods
that do not get better with other treatments, such as medicines. Signs that you
have a heavy period include that you:",
" </p>",
" <p>",
" <ul class=\"bulletCompact-block\">",
" <li>",
" Have a period that lasts more than 7 days",
" </li>",
" <li>",
" Have to change a pad or tampon every 1 or 2 hours",
" </li>",
" <li>",
" Pass large lumps of blood, called clots",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H261992057\">",
" <span class=\"h1\">",
" What happens during EA?",
" </span>",
" &nbsp;&mdash;&nbsp;Before the procedure, you will get medicines that block
pain. You might also get medicines to make you unconscious so you can&rsquo;t feel,
see, or hear anything during surgery.",
" </p>",
" <p>",
" Doctors use different techniques for EA. For most of these, the doctor puts
a device into your vagina and up into your uterus. The device uses heat, cold,
microwaves, or radio waves to scar the lining of your uterus.",
" </p>",
" <p>",
" Another technique is called &ldquo;electrosurgery.&rdquo; It uses a device
with an electric wire loop, a roller ball, or a spiked-ball tip to scar the lining
of the uterus.",
" </p>",
" <p class=\"headingAnchor\" id=\"H261992040\">",
" <span class=\"h1\">",
" What happens after endometrial ablation?",
" </span>",
" &nbsp;&mdash;&nbsp;After the surgery, you might have:",
" </p>",
" <p>",
" <ul class=\"bulletCompact-block\">",
" <li>",
" Cramps for 1 to 3 days",
" </li>",
" <li>",
" Light vaginal bleeding or pink vaginal discharge for 2 to 3 days",
" </li>",
" </ul>",
" </p>",
" <p>",
" In rare cases, EA causes heavy bleeding or a hole in the uterus.",
" </p>",
" <p>",
" You will probably be able to do your normal activities 1 to 3 days after the
surgery. Many women have irregular periods after the surgery. After 2 to 3 months,
most women have lighter periods and some stop having periods completely.",
" </p>",
" <p class=\"headingAnchor\" id=\"H261992023\">",
" <span class=\"h1\">",
" What if I want to get pregnant?",
" </span>",
" &nbsp;&mdash;&nbsp;Scarring in the uterus can make pregnancy unsafe for the
mother or baby. You should not have this procedure if you want to get pregnant. But
because women CAN still get pregnant after EA, doctors advise women who have the
procedure to use birth control afterwards.",
" </p>",
" <p class=\"headingAnchor\" id=\"H261992007\">",
" <span class=\"h1\">",
" More on this topic",
" </span>",
" </p>",
" <p>",
" <a class=\"medical medical_basics\" href=\"UTD.htm?14/25/14738?
source=see_link\">",
" Patient information: Heavy periods (The Basics)",
" </a>",
" <br/>",
" <a class=\"medical medical_basics\" href=\"UTD.htm?6/42/6818?
source=see_link\">",
" Patient information: Anesthesia (The Basics)",
" </a>",
" <br/>",
" <a class=\"medical medical_basics\" href=\"UTD.htm?20/52/21314?
source=see_link\">",
" Patient information: Uterine fibroids (The Basics)",
" </a>",
" </p>",
" <p>",
" <a class=\"medical medical_patient\" href=\"UTD.htm?22/35/23094?
source=see_link\">",
" Patient information: Menorrhagia (excessive menstrual bleeding) (Beyond the
Basics)",
" </a>",
" <br/>",
" <a class=\"medical medical_patient\" href=\"UTD.htm?22/18/22820?
source=see_link\">",
" Patient information: Abnormal uterine bleeding (Beyond the Basics)",
" </a>",
" <br/>",
" <a class=\"medical medical_patient\" href=\"UTD.htm?20/20/20804?
source=see_link\">",
" Patient information: Uterine fibroids (Beyond the Basics)",
" </a>",
" </p>",
" </div>",
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" Apr 20, 2013.",
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" What is endometrial ablation?",
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" Why might a woman get EA?",
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" <a class=\"medical medical_patient\" href=\"UTD.htm?20/20/20804?
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" Patient information: Uterine fibroids (Beyond the Basics)",
" </a>",
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