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var title_f0_11_176="Infectious mononucleosis (mono) in adults and adolescents";

var content_f0_11_176=[" <h1 id=\"patTopicTitle\">",


" Patient information: Infectious mononucleosis (mono) in adults and adolescents
(Beyond the Basics)",
" </h1>",
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" <a class=\"contributor contributor_credentials patTopicContributorsType\"
href=\"UTD.htm?0/11/176/contributors\">",
" Author",
" </a>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/11/176/contributors\" id=\"au7338\">",
" Paul G Auwaerter, MD, MBA, FACP",
" </a>",
" </td>",
" <td>",
" <a class=\"contributor contributor_credentials patTopicContributorsType\"
href=\"UTD.htm?0/11/176/contributors\">",
" Section Editors",
" </a>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/11/176/contributors\" id=\"se636\">",
" Martin S Hirsch, MD",
" </a>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/11/176/contributors\" id=\"se4413\">",
" Sheldon L Kaplan, MD",
" </a>",
" </td>",
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" <a class=\"contributor contributor_credentials patTopicContributorsType\"
href=\"UTD.htm?0/11/176/contributors\">",
" Deputy Editor",
" </a>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/11/176/contributors\" id=\"de1919\">",
" Anna R Thorner, MD",
" </a>",
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" <p class=\"headingAnchor\" id=\"H1\">",
" <span class=\"h1\">",
" INFECTIOUS MONONUCLEOSIS OVERVIEW",
" </span>",
" </p>",
" <p>",
" Infectious mononucleosis, also known as mono or \"the kissing disease,\" is
an infection that causes fever, sore throat, fatigue, and enlarged lymph nodes in
the neck. It most commonly occurs in adolescents and young adults. Although not
generally considered a serious illness, mononucleosis can lead to significant loss
of time from school or work due to profound fatigue.",
" </p>",
" <p>",
" This topic will discuss the symptoms, diagnosis, and treatment of
mononucleosis in adolescents and adults.",
" </p>",
" <p class=\"headingAnchor\" id=\"H2\">",
" <span class=\"h1\">",
" HOW DID I GET MONO?",
" </span>",
" </p>",
" <p>",
" Mono is caused by the Epstein-Barr virus (EBV), which can spread from person
to person through contact with saliva. Kissing or sharing of eating utensils or
drinking glasses with a person who is sick with mono should be avoided.",
" </p>",
" <p>",
" EBV infection most commonly occurs in young children, although most are not
ill when they develop mono. Symptomatic infection is much more common in teenagers
and young adults. Most people are exposed to EBV during childhood, although most
infected young children do not develop symptoms. Infection often leads to illness
in the 5 to 10 percent of adolescents and adults who have not been exposed to the
virus. That is why symptomatic disease is more common in teenagers and young
adults. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?13/55/14202?
source=see_link\">",
" \"Clinical manifestations and treatment of Epstein-Barr virus infection\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H3\">",
" <span class=\"h1\">",
" MONO SYMPTOMS",
" </span>",
" </p>",
" <p class=\"headingAnchor2\" id=\"H4\">",
" <span class=\"h2\">",
" Common symptoms",
" </span>",
" &nbsp;&mdash;&nbsp;It may take four to eight weeks after exposure to the
virus for the first symptoms (body aches, headache, low-grade fever) to appear. The
most common mono symptoms include:",
" </p>",
" <p>",
" <ul class=\"bulletCompact-block\">",
" <li>",
" Fever (temperature greater than 100.4&ordm;F or 38&ordm;C)",
" </li>",
" <li>",
" Sore throat",
" </li>",
" <li>",
" Enlarged lymph nodes (glands) in the neck",
" </li>",
" <li>",
" Fatigue, which may be severe and can occasionally last for months",
" </li>",
" </ul>",
" </p>",
" <p>",
" Some people have all of these symptoms while others have only one or two
symptoms, such as sore throat or fever and enlarged lymph nodes. Young children and
older adults may have only a fever and muscle aches. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?30/18/31018?
source=see_link\">",
" \"Infectious mononucleosis in adults and adolescents\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor2\" id=\"H5\">",
" <span class=\"h2\">",
" Enlargement of the spleen",
" </span>",
" &nbsp;&mdash;&nbsp;The spleen is an organ in the left upper abdomen, just
under the diaphragm (",
" <a class=\"graphic graphic_figure graphicRef61816 \" href=\"UTD.htm?
36/5/36948\">",
" figure 1",
" </a>",
" ). It becomes enlarged in about half of people with mono. If the spleen
becomes enlarged, doctors recommend avoiding sports activities or heavy lifting for
a few weeks. This advice is given to avoid the rare complication of splenic rupture
that can occur after trauma. Symptoms of rupture include sudden, sharp pain in the
abdomen. This is a potentially life-threatening complication that requires
immediate medical treatment. (See",
" <a class=\"local\" href=\"#H11\">",
" 'When can I go back to work or school?'",
" </a>",
" below.)",
" </p>",
" <p class=\"headingAnchor\" id=\"H6\">",
" <span class=\"h1\">",
" HOW IS MONO DIAGNOSED?",
" </span>",
" </p>",
" <p>",
" Mono may be suspected based upon a person's symptoms and physical
examination. Blood tests are done to confirm the diagnosis. However, blood tests
can be falsely negative during the first weeks of symptoms.",
" </p>",
" <p class=\"headingAnchor\" id=\"H7\">",
" <span class=\"h1\">",
" MONO TREATMENT",
" </span>",
" </p>",
" <p>",
" The goal of mono treatment is to ease the symptoms while the immune system
contains the initial viral infection. Antibiotics are not helpful because mono is
caused by a virus and there are no antiviral medications that can treat or cure
EBV.",
" </p>",
" <p class=\"headingAnchor2\" id=\"H8\">",
" <span class=\"h2\">",
" Pain and fever",
" </span>",
" &nbsp;&mdash;&nbsp;Sore throat, muscle aches, and fever can be treated with
non-prescription medications, such as acetaminophen (Tylenol&reg; and others) or
ibuprofen (Motrin&reg;, Advil&reg;). Acetaminophen is broken down by the liver.
Thus, it is important to closely follow the dosing instructions or your healthcare
provider's instructions to safely take this medication. Acetaminophen and ibuprofen
are also recommended for use in children. Aspirin should not be given to young
children with mono because of possible liver complications.",
" </p>",
" <p class=\"headingAnchor2\" id=\"H9\">",
" <span class=\"h2\">",
" Rest",
" </span>",
" &nbsp;&mdash;&nbsp;Mono can cause severe fatigue, although most people
recover within two to four weeks. For some, significant tiredness lasts for weeks
to months. Early in the infection, it is important to get adequate rest, although
complete bed rest is not necessary.",
" </p>",
" <p class=\"headingAnchor2\" id=\"H10\">",
" <span class=\"h2\">",
" Diet",
" </span>",
" &nbsp;&mdash;&nbsp;Feeling ill often causes a loss of appetite. This is
normal, and usually improves as the infection improves. It is important, even if
you have no appetite, to drink an adequate amount of fluids. This is especially
true if you are taking ibuprofen for pain or fever because ibuprofen can affect
kidney function if you become dehydrated. You are drinking adequate fluids if your
urine is a pale yellow color.",
" </p>",
" <p class=\"headingAnchor\" id=\"H11\">",
" <span class=\"h1\">",
" WHEN CAN I GO BACK TO WORK OR SCHOOL?",
" </span>",
" </p>",
" <p>",
" Many people with mono develop an enlarged spleen, which can last for a few
weeks or longer. Although you can return to school or work when you are feeling
better, it's important to avoid activities that can cause injury to the spleen.",
" </p>",
" <p>",
" Experts generally recommend that athletes not participate in sports
activities for at least the first three to four weeks of the illness [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/176/abstract/1\">",
" 1",
" </a>",
" ]. Your healthcare provider should determine when it is safe for you to
participate in strenuous activities or contact sports.",
" </p>",
" <p>",
" When you do begin participating in sports activities again, we recommend
starting slowly, increasing activity gradually. Even highly trained athletes may
not feel as fit after having mono as they did before the illness.",
" </p>",
" <p class=\"headingAnchor\" id=\"H12\">",
" <span class=\"h1\">",
" WHEN WILL I FEEL BETTER?",
" </span>",
" </p>",
" <p>",
" Most people who suffer with mono recover completely without any long-term
complications. Symptoms usually begin to improve within one to two weeks.",
" </p>",
" <p class=\"headingAnchor\" id=\"H13\">",
" <span class=\"h1\">",
" WHERE TO GET MORE INFORMATION",
" </span>",
" </p>",
" <p>",
" Your healthcare provider is the best source of information for questions and
concerns related to your medical problem.",
" </p>",
" <p>",
" This article will be updated as needed on our web site (",
" <a class=\"external\" href=\"file://www.uptodate.com/patients\">",
" www.uptodate.com/patients",
" </a>",
" ). Related topics for patients, as well as selected articles written for
healthcare professionals, are also available. Some of the most relevant are listed
below.",
" </p>",
" <p class=\"headingAnchor2\" id=\"H2875571\">",
" <span class=\"h2\">",
" Patient level information",
" </span>",
" &nbsp;&mdash;&nbsp;UpToDate offers two types of patient education
materials.",
" </p>",
" <p class=\"headingAnchor2\" id=\"H2875586\">",
" <span class=\"h3\">",
" The Basics",
" </span>",
" &nbsp;&mdash;&nbsp;The Basics patient education pieces 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.",
" </p>",
" <p>",
" <a class=\"medical medical_basics\" href=\"UTD.htm?40/33/41489?
source=see_link\">",
" Patient information: Mono, the &ldquo;kissing disease&rdquo; (The Basics)",
" </a>",
" <br/>",
" <a class=\"medical medical_basics\" href=\"UTD.htm?42/59/43955?
source=see_link\">",
" Patient information: Swollen neck nodes in children (The Basics)",
" </a>",
" <br/>",
" <a class=\"medical medical_basics\" href=\"UTD.htm?19/10/19618?
source=see_link\">",
" Patient information: Cytomegalovirus (The Basics)",
" </a>",
" <br/>",
" <a class=\"medical medical_basics\" href=\"UTD.htm?35/31/36338?
source=see_link\">",
" Patient information: When to worry about a fever (The Basics)",
" </a>",
" </p>",
" <p class=\"headingAnchor2\" id=\"H2875594\">",
" <span class=\"h3\">",
" Beyond the Basics",
" </span>",
" &nbsp;&mdash;&nbsp;Beyond the Basics patient education pieces are longer,
more sophisticated, and more detailed. These articles are best for patients who
want in-depth information and are comfortable with some medical jargon.",
" </p>",
" <p>",
" This topic currently has no corresponding Basic content.",
" </p>",
" <p class=\"headingAnchor2\" id=\"H14\">",
" <span class=\"h2\">",
" Professional level information",
" </span>",
" &nbsp;&mdash;&nbsp;Professional level articles are designed to keep doctors
and other health professionals up-to-date on the latest medical findings. These
articles are thorough, long, and complex, and they contain multiple references to
the research on which they are based. Professional level articles are best for
people who are comfortable with a lot of medical terminology and who want to read
the same materials their doctors are reading.",
" </p>",
" <p>",
" <a class=\"medical medical_review\" href=\"UTD.htm?13/55/14202?
source=see_link\">",
" Clinical manifestations and treatment of Epstein-Barr virus infection",
" </a>",
" <br/>",
" <a class=\"medical medical_review\" href=\"UTD.htm?8/25/8597?
source=see_link\">",
" Diagnosis of cytomegalovirus",
" </a>",
" <br/>",
" <a class=\"medical medical_review\" href=\"UTD.htm?13/25/13722?
source=see_link\">",
" Epidemiology, clinical manifestations, and treatment of cytomegalovirus
infection in immunocompetent hosts",
" </a>",
" <br/>",
" <a class=\"medical medical_review\" href=\"UTD.htm?5/38/5738?
source=see_link\">",
" Evaluation of acute pharyngitis in adults",
" </a>",
" <br/>",
" <a class=\"medical medical_review\" href=\"UTD.htm?30/18/31018?
source=see_link\">",
" Infectious mononucleosis in adults and adolescents",
" </a>",
" <br/>",
" </p>",
" <p>",
" [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/176/abstract/1-4\">",
" 1-4",
" </a>",
" ]",
" </p>",
" </div>",
" </div>",
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" Literature review current through:",
" </span>",
" Oct 2013.",
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" |",
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" This topic last updated:",
" </span>",
" Oct 11, 2011.",
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physician or",
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" </div>",
" <ol id=\"reference\">",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/11/176/abstract/1\">",
" Putukian M, O'Connor FG, Stricker P, et al. Mononucleosis and athletic
participation: an evidence-based subject review. Clin J Sport Med 2008; 18:309.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/11/176/abstract/2\">",
" Fafi-Kremer S, Morand P, Brion JP, et al. Long-term shedding of infectious
epstein-barr virus after infectious mononucleosis. J Infect Dis 2005; 191:985.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/11/176/abstract/3\">",
" Vetsika EK, Callan M. Infectious mononucleosis and Epstein-Barr virus.
Expert Rev Mol Med 2004; 6:1.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/11/176/abstract/4\">",
" Higgins CD, Swerdlow AJ, Macsween KF, et al. A study of risk factors for
acquisition of Epstein-Barr virus and its subtypes. J Infect Dis 2007; 195:474.",
" </a>",
" </li>",
" </ol>",
" </div>",
" </div>",
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" <a href=\"#H1\">",
" INFECTIOUS MONONUCLEOSIS OVERVIEW",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#H2\">",
" HOW DID I GET MONO?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#H3\">",
" MONO SYMPTOMS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#H6\">",
" HOW IS MONO DIAGNOSED?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#H7\">",
" MONO TREATMENT",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#H11\">",
" WHEN CAN I GO BACK TO WORK OR SCHOOL?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#H12\">",
" WHEN WILL I FEEL BETTER?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#H13\">",
" WHERE TO GET MORE INFORMATION",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#references\">",
" REFERENCES",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" GRAPHICS",
" </h1>",
" <div id=\"relatedGraphics\">",
" <ul>",
" <li class=\"plainItem\">",
" FIGURES",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_figure\" href=\"UTD.htm?36/5/36948\"
title=\"figure 1\">",
" Spleen anatomy PI",
" </a>",
" </li>",
" </ul>",
" </div>",
" </div>",
" </div>",
" </div>",
" </div>",
" </div>",
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var title_f0_11_177="Painful arc sign for rotator cuff pathology";
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" Painful arc sign for rotator cuff pathology",
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" </div>",
" <div class=\"lgnd\">",
" Pain with active abduction beyond 90 degrees (ie, painful arc sign) suggests
rotator cuff tendinopathy. The test is most useful when combined with other rotator
cuff tests, such as the Neer and Hawkins-Kennedy tests.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Courtesy of Stephen Simons, MD, J Bryan Dixon, MD, and David Kruse, MD",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
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" &copy;2013 UpToDate",
" <sup>",
" &reg;",
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" <div id=\"graphicsLinks\">",
" <a href=\"?imageKey=OBGYN
%2F64192&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
%2F64192&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: 615px\">",
" <div class=\"ttl\">",
" Combined Bakri balloon, plus Bilateral Looped Uterine Vessels Sutures (B-LUVS)
technique in case of cesarean delivery.",
" </div>",
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" </div>",
" <div class=\"lgnd\">",
" (A) The double loop suture technique should include the full thickness of the
lateral uterine wall. For the first stitch, the needle is brought through the eye
of the loop, thus eliminating the need for a knot.",
" <br>",
" (B) The looped sutures are placed stepwise up the side of the uterus
bilaterally, including both lower and upper uterine segments. The loop is cut prior
to the last stitch, the last stitch is taken and the two ends are tied. The balloon
catheter is inserted at this time.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Courtesy of Younes N Bakri, MD.",
" </div>",
" </br>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f0_11_178=[""].join("\n");
var outline_f0_11_178=null;
var title_f0_11_179="Schuknecht foreign body remover";
var content_f0_11_179=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" <sup>",
" &reg;",
" </sup>",
" </div>",
" <div id=\"graphicsLinks\">",
" <a href=\"?imageKey=EM
%2F86356&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=EM
%2F86356&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: 524px\">",
" <div class=\"ttl\">",
" Schuknecht foreign body remover",
" </div>",
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;\">",
" </div>",
" <div class=\"lgnd\">",
" Suction attaches to the bottom of the red handle to permit removal of freely
mobile spherical foreign bodies from the external auditory canal or nasal cavity.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Courtesy of Glenn C Isaacson, MD.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f0_11_179=[""].join("\n");
var outline_f0_11_179=null;
var title_f0_11_180="Endomyocard fibros RA echo";
var content_f0_11_180=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" <sup>",
" &reg;",
" </sup>",
" </div>",
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" <a href=\"?imageKey=CARD
%2F53361&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=2\" onclick=\"\">",
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" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=CARD
%2F53361&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=2\" onclick=\"\"
title=\"Print this page\">",
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" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
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" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 539px\">",
" <div class=\"ttl\">",
" Endomyocardial fibrosis",
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" </div>",
" <div class=\"lgnd\">",
" A) Surface echocardiogram with right ventricular apical fibrosis and severe
right atrial enlargement. B) Left ventriculogram with severe mitral regurgitation
and apical obliteration.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" A) Reproduced with permission from Salemi VM, Rochitte CE, Barbosa MM, Mady
C. Images in cardiology. Clinical and echocardiographic dissociation in a patient
with right ventricular endomyocardial fibrosis. Heart 2005; 91:1399. Copyright
&copy;2005 BMJ Publishing Group.",
" <br>",
" B) Reproduced with permission from: Joshi R, Abraham S, Kumar AS. New
approach for complete endocardiectomy in left ventricular endomyocardial fibrosis.
J Thorac Cardiovasc Surg 2003; 125:40. Copyright &copy;2003 American Association
for Thoracic Surgery.",
" </br>",
" </div>",
" </div>",
" </div>",
" </div>",
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" </div>",
" <div class=\"lgnd\">",
" Upper left panel: axial T1 weighted MR image with contrast; upper right panel:
axial T2, weighted MR image; lower left panel: T1 weighted sagittal MR image with
contrast; lower right panel: magnetic resonance spectra of a patient with a diffuse
pontine glioma (see arrows).",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f0_11_181=[""].join("\n");
var outline_f0_11_181=null;
var title_f0_11_182="DLBCL BCL-6 staining";
var content_f0_11_182=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" <sup>",
" &reg;",
" </sup>",
" </div>",
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" <a href=\"?imageKey=HEME
%2F53759&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=HEME
%2F53759&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: 524px\">",
" <div class=\"ttl\">",
" Diffuse large B-cell lymphoma BCL-6 staining",
" </div>",
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" </div>",
" <div class=\"lgnd\">",
" Diffuse large B-cell lymphoma, centroblast variant, with nuclear BCL-6
staining of numerous cells. BCL-6/peroxidase stain.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Reproduced with permission from: Ioachim HL, Medeiros LJ. Diffuse large B-
cell lymphoma. In: Ioachim's Lymph Node Pathology, 4th ed, Lippincott Williams
&amp; Wilkins, Philadelphia 2009. Copyright &copy; 2009 Lippincott Williams &amp;
Wilkins.",
" </div>",
" <div class=\"contractual\">",
" <br/>",
" <a href=\"file://www.lww.com\">",
" file://www.lww.com",
" </a>",
" </div>",
" </div>",
" </div>",
" </div>",
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" </div>",
" <div class=\"lgnd\">",
" 51-year-old woman with short Roux limb misconstruction. For upper
gastrointestinal examination, medium-density barium was administered through
gastric tube in excluded gastric segment. Fluoroscopic image shows distal portion
of stomach (asterisk) and biliary limb (arrowheads) are unremarkable. At distal
anastomosis, preferential flow of contrast material into alimentary limb (white
arrows) is evident with little contrast material passing distally into common limb
(black arrow). Antegrade assessment of alimentary limb was limited owing to
concomitant proximal anastomotic stenosis (not shown). At surgery, Roux limb
measuring only 25 cm was identified. Short length allowed retrograde reflux,
resulting in Roux-en-O physiologic characteristics.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Reprinted with the permission of the American Journal of Roentgenology.
Mitchell MT, Gasparaitis AE, Alverdy JC. Imaging findings in roux-en-o and other
misconstructions: Rare but serious complications of roux-en-y gastric bypass
surgery. AJR Am J Roentgenol 2008; 190:367. Copyright &copy; 2008 American Roentgen
Ray Society.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f0_11_183=[""].join("\n");
var outline_f0_11_183=null;
var title_f0_11_184="Disease outcome and functional capacity in rheumatoid
arthritis";
var content_f0_11_184=[" <noscript>",
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" <!-- TC:TOPIC_PAGE -->",
" <div id=\"topicContent\">",
" <div id=\"topicTitle\">",
" Disease outcome and functional capacity in rheumatoid arthritis",
" </div>",
" <div id=\"topicContributors\">",
" <div>",
" <a id=\"authors\">",
" </a>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?0/11/184/contributors\">",
" Authors",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/11/184/contributors\">",
" PJW Venables, MA, MB BChir, MD, FRCP",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/11/184/contributors\">",
" RN Maini, BA, MB BChir, FRCP, FMedSci, FRS",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?0/11/184/contributors\">",
" Section Editor",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/11/184/contributors\">",
" James R O'Dell, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?0/11/184/contributors\">",
" Deputy Editor",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/11/184/contributors\">",
" Paul L Romain, MD",
" </a>",
" <br/>",
" </div>",
" </div>",
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" <a href=\"UTD.htm?0/11/184/contributor-disclosure\" target=\"_blank\">",
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" All topics are updated as new evidence becomes available and our",
" </span>",
" <a href=\"/home/editorial-policy\" target=\"_blank\">",
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" 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>",
" Apr 17, 2012.",
" </div>",
" <div id=\"topicText\">",
" <p class=\"headingAnchor\" id=\"H1\">",
" <span class=\"h1\">",
" INTRODUCTION",
" </span>",
" &nbsp;&mdash;&nbsp;The course of RA is variable [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/1\">",
" 1",
" </a>",
" ]. Approximately 15 to 20 percent of patients have intermittent disease with
periods of exacerbation and a relatively good prognosis. However, most patients
have progressive disease, with either a slow or a rapid course. The outcome of RA
is dependent upon the degree of joint damage, the physical functional status of the
patient, psychological health, and the presence of comorbid illness such as
cardiovascular disease, infection, and B cell lymphomas. A reduced life expectancy
is seen in some patients with severe RA, due to illnesses that may be the result of
RA itself or to the drugs used in its treatment (",
" <a class=\"graphic graphic_table graphicRef82537 \" href=\"UTD.htm?
26/45/27355\">",
" table 1",
" </a>",
" ).",
" </p>",
" <p>",
" Functional capacity, comorbidities, and mortality in RA are reviewed here.
Cardiovascular and renal diseases associated with RA are discussed elsewhere.
(See",
" <a class=\"medical medical_review\" href=\"UTD.htm?30/44/31433?
source=see_link\">",
" \"Coronary artery disease in rheumatoid arthritis: Diagnostic and therapeutic
implications\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?10/24/10631?
source=see_link\">",
" \"Coronary artery disease in rheumatoid arthritis: Epidemiology,
pathogenesis, and risk factors\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?26/21/26968?
source=see_link\">",
" \"Heart failure and left ventricular dysfunction in rheumatoid arthritis\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/59/37812?
source=see_link\">",
" \"Renal disease in patients with rheumatoid arthritis\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H2\">",
" <span class=\"h1\">",
" FUNCTIONAL CAPACITY",
" </span>",
" &nbsp;&mdash;&nbsp;Loss of functional capacity in RA is a result of the
summation of loss of function in individual joints. Individual joint function
depends upon numerous factors:",
" </p>",
" <p>",
" <ul class=\"bulletCompact-block\">",
" <li>",
" Severity of disease activity",
" </li>",
" <li>",
" Structural integrity of a joint",
" </li>",
" <li>",
" Muscle strength and tone",
" </li>",
" <li>",
" General fitness of the patient",
" </li>",
" <li>",
" Psychosocial factors",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H3\">",
" <span class=\"h2\">",
" Assessment",
" </span>",
" &nbsp;&mdash;&nbsp;Since functional capacity is an important determinant of
the natural history of RA and is a useful tool for assessing the effectiveness of
therapeutic interventions, many instruments for patient evaluation have been
developed.",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Attempts have been made to classify and grade functional capacity based upon
the patient's ability to undertake daily activities in the home, at work, or during
leisure time. Restriction of physical activity, use of aids and appliances,
personal assistance, and level of independence are taken into account in one widely
used classification (",
" <a class=\"graphic graphic_table graphicRef59908 \" href=\"UTD.htm?
7/33/7707\">",
" table 2",
" </a>",
" ) [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/2\">",
" 2",
" </a>",
" ].",
" </li>",
" <li>",
" Functional disability indices are also based on self-report questionnaires,
which have been validated, such as the Stanford Health Assessment Questionnaire
(HAQ) [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/3,4\">",
" 3,4",
" </a>",
" ] and the Arthritis Impact Measurement Scale Health Status Questionnaire
(AIMS) [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/5\">",
" 5",
" </a>",
" ]. The complexity of these questionnaires and the time required for
completion has led to their modification and simplification for use in routine
management [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/6\">",
" 6",
" </a>",
" ]. Functional disability is predominantly due to inflammatory synovitis
during the early stage of the disease, loss of structural integrity of joints at a
late stage, and, depending upon the level of disease activity, a combination of
both for the rest of the course of disease [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/7,8\">",
" 7,8",
" </a>",
" ].",
" </li>",
" </ul>",
" </p>",
" <p>",
" Although the HAQ is copyrighted, an English-language version is generally
available free of charge when permission is requested to use it [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/4\">",
" 4",
" </a>",
" ]. The HAQ questionnaires and instructions are available from the Stanford
University Medical Center on the internet for investigators and practitioners at:",
" <a class=\"external\" href=\"file://aramis.stanford.edu/HAQ.html\">",
" file://aramis.stanford.edu/HAQ.html",
" </a>",
" (accessed April 12, 2012).",
" </p>",
" <p>",
" These questionnaires are limited, however, by their emphasis on the physical
impact of RA, rather than the psychological health of the patient or the familial,
social, and financial consequences of the disease. Indeed, further studies have
suggested that psychosocial factors may contribute between 10 to 20 percent towards
disability [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/7,9\">",
" 7,9",
" </a>",
" ]. All of these important issues contribute to the patient's quality of life
[",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/10\">",
" 10",
" </a>",
" ]. Thus, a holistic approach to managing patients with RA requires careful
attention to many potential consequences of this chronic disease.",
" </p>",
" <p class=\"headingAnchor\" id=\"H4\">",
" <span class=\"h2\">",
" Disability due to RA",
" </span>",
" &nbsp;&mdash;&nbsp;While recognizing the limitations of self-reports of
physical function, there is evidence that the common-sense notion that the
combination of inflammation and joint damage leads to functional difficulty is
correct. This was illustrated by the results of a Finnish population-based survey
of 1095 patients with an established diagnosis of RA and 1530 age and gender
matched controls [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/11\">",
" 11",
" </a>",
" ]. A score on the HAQ of more than 1 suggests that a person is having
difficulty with most activities of daily living. Patients were nearly eight times
more likely to report moderate disability (HAQ score &ge;1) than controls.",
" </p>",
" <p class=\"headingAnchor\" id=\"H5\">",
" <span class=\"h2\">",
" Long-term outcomes",
" </span>",
" &nbsp;&mdash;&nbsp;The long-term functional outlook is variable for patients
who present early in the course of their illness and are treated. As an example, in
one study that prospectively followed 168 Swedish patients for 10 years or more, 94
percent continued to be independent in their daily activities [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/12\">",
" 12",
" </a>",
" ]. The proportions of those with disabilities described as based upon HAQ
scores as &ldquo;almost no,&rdquo; mild, moderate, and serious were 20, 28, 48, and
10 percent, respectively, at the end of observation. Almost 20 percent of patients
had quiescent disease when last examined.",
" </p>",
" <p>",
" Use of effective disease modifying antirheumatic drugs has been increasing,
and this may be having a favorable effect on the severity of disability of patients
with RA. This was illustrated in a long-term study of successive cohorts of
patients with RA that included 3035 patients from eight centers in North America
who were followed from 1977 to 1998 [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/13\">",
" 13",
" </a>",
" ]. Use of",
" <a class=\"drug drug_general\" href=\"UTD.htm?23/38/24170?source=see_link\">",
" methotrexate",
" </a>",
" (MTX) at enrollment, considered to be an indicator for effective DMARD
therapy, increased from 1 to 44 percent, while",
" <a class=\"drug drug_general\" href=\"UTD.htm?37/43/38585?source=see_link\">",
" prednisone",
" </a>",
" use remained relatively constant (31 to 33 percent among the initial and final
cohorts, respectively). Average disability as measured by HAQ declined by
approximately 2 percent per year. The long-term decline in disability was not
explained by other patient characteristics (ie, age, gender, race, level of
education, disease duration, or length of follow-up). After adjustment for all
recognized confounders, the mean decrease in HAQ disability remained 2 percent per
year.",
" </p>",
" <p>",
" The beneficial effects of antirheumatic drug treatment on function may be
determined, at least in part, by the amount of joint damage that is present at the
time such therapy is initiated. This was illustrated in retrospective study data
from two trials that had randomly assigned patients with moderate to severe RA, who
had not responded fully to MTX, to receive either",
" <a class=\"drug drug_general\" href=\"UTD.htm?28/6/28776?source=see_link\">",
" infliximab",
" </a>",
" or placebo [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/14,15\">",
" 14,15",
" </a>",
" ]; improvement in function as measured by HAQ was inversely correlated with
the amount of baseline radiographic damage [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/16\">",
" 16",
" </a>",
" ]. These findings suggest that interventions that are effective in preventing
joint damage may be most effective in improving function when introduced as early
as possible. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?38/11/39098?
source=see_link\">",
" \"General principles of management of rheumatoid arthritis in adults\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H6\">",
" <span class=\"h2\">",
" Impact on employment",
" </span>",
" &nbsp;&mdash;&nbsp;The impact of RA on the ability to earn a living is
uncertain. Early studies suggested that employment of patients with RA was
approximately one-half that of unaffected individuals. However, subsequent surveys
report similar employment rates among patients with or without RA. As an example,
after adjustment for level of education, gender, and age among individuals in the
Netherlands, the rates of employment for patients with RA compared with that of the
general population were not significantly different (61 versus 65 percent,
respectively) [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/17\">",
" 17",
" </a>",
" ]. The following features related to RA have been noted to increase the
likelihood of being unable to work [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/18-20\">",
" 18-20",
" </a>",
" ]:",
" </p>",
" <p>",
" <ul class=\"bulletCompact-block\">",
" <li>",
" Pain",
" </li>",
" <li>",
" Impaired physical function",
" </li>",
" <li>",
" Difficulty commuting to work",
" </li>",
" <li>",
" Failure of antirheumatic drug therapy to produce significant improvement
(eg, American College of Rheumatology 20 percent response [ACR20]) and Disease
Activity Scores (eg, DAS28)",
" </li>",
" </ul>",
" </p>",
" <p>",
" The presence of other factors is significantly associated with a decreased
risk of being disabled, including [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/18,20\">",
" 18,20",
" </a>",
" ]:",
" </p>",
" <p>",
" <ul class=\"bulletCompact-block\">",
" <li>",
" Being self-employed",
" </li>",
" <li>",
" Having ergonomic improvements made at the work site",
" </li>",
" <li>",
" Reporting a positive attitude about the importance of work",
" </li>",
" <li>",
" Having at least an ACR20 response to antirheumatic therapy",
" </li>",
" </ul>",
" </p>",
" <p>",
" Employment status (ie, whether a patient is working or not) does not fully
capture the economic impact of the disease as it relates to the workplace. The
productivity of patients who continue to work may be adversely affected by disease-
related absences and work restrictions. An instrument for assessment of work-
related limitations, the Work Limitations Questionnaire (WLQ), may be useful for
measuring the impact of RA treatments and workplace interventions on productivity
[",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/21,22\">",
" 21,22",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H7\">",
" <span class=\"h1\">",
" COMORBIDITY AND MORTALITY",
" </span>",
" &nbsp;&mdash;&nbsp;Patients with RA have an increased prevalence of other
serious illnesses. As an example, one study of 288 patients with RA found that 54
of the respondents reported other chronic conditions; 20 rated at least one of
these other conditions as severe [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/23\">",
" 23",
" </a>",
" ]. The predominant conditions contributing to the comorbidity and mortality of
RA are infections, renal impairment, lymphomas, and cardiovascular disease (",
" <a class=\"graphic graphic_table graphicRef82537 \" href=\"UTD.htm?
26/45/27355\">",
" table 1",
" </a>",
" ) [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/23\">",
" 23",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H8\">",
" <span class=\"h2\">",
" Infection",
" </span>",
" &nbsp;&mdash;&nbsp;Infections, particularly pulmonary, skin, and joint
infections, occur with increased frequency in RA [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/24\">",
" 24",
" </a>",
" ]. The reason is incompletely understood, but the following factors may
contribute [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/25\">",
" 25",
" </a>",
" ]:",
" </p>",
" <p>",
" <ul class=\"bulletCompact-block\">",
" <li>",
" Immunosuppression by the disease itself or its treatment",
" </li>",
" <li>",
" The presence (often subclinical) of inflammatory lung disease",
" </li>",
" <li>",
" An increase in cigarette smoking",
" </li>",
" <li>",
" Multiple factors associated with disability and immobility",
" </li>",
" </ul>",
" </p>",
" <p>",
" Immunosuppression from corticosteroids and immunosuppressive agents is
probably the most important [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/26\">",
" 26",
" </a>",
" ]. However, the highest glucocorticoid doses are used in the patients with
most active disease, which also may contribute to the infection risk. Consistent
with this hypothesis is the observation in a population-based study of 609 RA
patients and an equal number of controls that, after adjustment for corticosteroid
use, leukopenia, age, cigarette smoking, and diabetes, RA remained an independent
risk factor for infection [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/24\">",
" 24",
" </a>",
" ]. The adjusted relative risk (hazard ratio) of infection that required
hospitalization was 1.83 for RA patients versus controls (95% CI 1.52-2.21). (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?26/47/27386?
source=see_link&amp;anchor=H6573898#H6573898\">",
" \"Major side effects of systemic glucocorticoids\", section on 'Infection and
immune response'",
" </a>",
" .)",
" </p>",
" <p>",
" In contrast to the increased risk of infection associated with the use of
glucocorticoids and potent immunosuppressives (discussed above), the use of
nonbiologic disease modifying antirheumatic drugs (DMARDs) does not appear to be
associated with an increased risk of infection. This was illustrated in a
retrospective study of 27,710 Canadian patients with RA [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/27\">",
" 27",
" </a>",
" ]. Among patients who were not taking glucocorticoids, the relative risk (RR)
of serious infection for DMARD users was not significantly different from that for
nonusers (adjusted RR for DMARD users 0.92 [95% CI 0.88-1.0]). All available
biologic DMARDs are associated with an increased risk of infections.",
" </p>",
" <p>",
" Neutropenia and increased susceptibility to infection are consequences of both
Felty's syndrome and the large granular lymphocyte syndrome. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?4/9/4247?
source=see_link\">",
" \"Clinical manifestations and diagnosis of Felty's syndrome\"",
" </a>",
" .) Even in the absence of the full-blown syndrome, mild lymphopenia is very
common in RA and may increase the susceptibility to infection.",
" </p>",
" <p class=\"headingAnchor\" id=\"H9\">",
" <span class=\"h2\">",
" Renal disease",
" </span>",
" &nbsp;&mdash;&nbsp;Renal disease is uncommon but may be due to RA itself or to
drug therapy. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/59/37812?
source=see_link\">",
" \"Renal disease in patients with rheumatoid arthritis\"",
" </a>",
" .) The renal disorders include:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Membranous nephropathy, which may be due to gold,",
" <a class=\"drug drug_general\" href=\"UTD.htm?4/6/4200?source=see_link\">",
" penicillamine",
" </a>",
" , RA, or nonsteroidal antiinflammatory drugs (see",
" <a class=\"medical medical_review\" href=\"UTD.htm?18/54/19306?
source=see_link\">",
" \"Causes and diagnosis of membranous nephropathy\"",
" </a>",
" )",
" </li>",
" <li>",
" Secondary (AA) amyloidosis due to the chronic inflammation (see",
" <a class=\"medical medical_review\" href=\"UTD.htm?32/14/33000?
source=see_link\">",
" \"Causes and diagnosis of secondary (AA) amyloidosis and relation to
rheumatic diseases\"",
" </a>",
" )",
" </li>",
" <li>",
" Focal mesangial proliferative glomerulonephritis of uncertain etiology,
which can occur in 5 to 10 percent of patients",
" </li>",
" <li>",
" NSAID nephrotoxicity including acute interstitial nephritis, which often
occurs in conjunction with the nephrotic syndrome due to minimal change disease.
Chronic NSAID therapy can also infrequently cause papillary necrosis. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?24/0/24582?
source=see_link\">",
" \"NSAIDs: Acute kidney injury (acute renal failure) and nephrotic
syndrome\"",
" </a>",
" .)",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H10\">",
" <span class=\"h2\">",
" Lymphoproliferative disorders",
" </span>",
" &nbsp;&mdash;&nbsp;Lymphoproliferative disorders occur with increased
frequency in patients with RA; incidence and mortality rates due to leukemia or
lymphoma are approximately twofold higher than expected [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/28-32\">",
" 28-32",
" </a>",
" ]. The lymphoma incidence increases as active RA persists and correlates with
the severity of disease activity. As an example, in a retrospective case-controlled
analysis of 378 Swedish RA patients with lymphoma and 378 matched RA controls, the
risk of lymphoma, expressed as an odds ratio (OR), increased dramatically (OR ninth
decile of disease activity, 9.4 [95% CI 3.1-28.0], OR tenth decile 61.6 [95% CI
21.0-181.0]) [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/33\">",
" 33",
" </a>",
" ]. The most common type of lymphoma was of the diffuse large B cell type (48
percent); 12 percent of lymphomas were positive when tested for the presence of
Epstein-Barr virus.",
" </p>",
" <p>",
" Drugs used to treat the disease, including alkylating agents,",
" <a class=\"drug drug_general\" href=\"UTD.htm?38/3/38967?source=see_link\">",
" azathioprine",
" </a>",
" , MTX, and anti-tumor necrosis factor alpha therapy, may contribute to the
risk [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/34\">",
" 34",
" </a>",
" ], although not all patients with RA who develop malignancies have been
treated with any of these drugs. In a case-control study of 23,810 patients with
RA, an increased risk of developing hematologic malignancies was associated with
the use of immunosuppressive agents; the relative risks were 1.18, 1.44, and 2.21
for",
" <a class=\"drug drug_general\" href=\"UTD.htm?23/38/24170?source=see_link\">",
" methotrexate",
" </a>",
" , azathioprine, and",
" <a class=\"drug drug_general\" href=\"UTD.htm?9/20/9546?source=see_link\">",
" cyclophosphamide",
" </a>",
" , respectively [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/35\">",
" 35",
" </a>",
" ]. The etiology of neoplasia in such patients may include immune
dysregulation",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" chronic immune activation. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?24/32/25098?
source=see_link\">",
" \"General toxicity of cyclophosphamide and chlorambucil in inflammatory
diseases\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?9/63/10232?
source=see_link\">",
" \"Pharmacology and side effects of azathioprine when used in rheumatic
diseases\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?10/61/11223?
source=see_link\">",
" \"Major side effects of low-dose methotrexate\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?3/19/3384?
source=see_link\">",
" \"Overview of biologic agents in the rheumatic diseases\"",
" </a>",
" .)",
" </p>",
" <p>",
" Up to one-third of patients with the large granular lymphocyte (LGL) syndrome
also have RA and may fulfill the clinical criteria for Felty's syndrome [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/36\">",
" 36",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?4/62/5095?
source=see_link\">",
" \"Large granular lymphocyte leukemia in rheumatoid arthritis\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H11\">",
" <span class=\"h2\">",
" Cardiovascular disease",
" </span>",
" &nbsp;&mdash;&nbsp;Observational studies suggest that RA is associated with an
increased risk of cardiovascular disease that appears to correlate with the
activity and duration of the RA. This issue is discussed in detail separately.
(See",
" <a class=\"medical medical_review\" href=\"UTD.htm?30/44/31433?
source=see_link\">",
" \"Coronary artery disease in rheumatoid arthritis: Diagnostic and therapeutic
implications\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?10/24/10631?
source=see_link\">",
" \"Coronary artery disease in rheumatoid arthritis: Epidemiology,
pathogenesis, and risk factors\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?26/21/26968?
source=see_link\">",
" \"Heart failure and left ventricular dysfunction in rheumatoid arthritis\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H12\">",
" <span class=\"h2\">",
" Mortality",
" </span>",
" &nbsp;&mdash;&nbsp;RA is a potentially fatal illness [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/13,29,37-39\">",
" 13,29,37-39",
" </a>",
" ]. One 1994 study, for example, followed 3501 patients with RA for up to 35
years and found that mortality was increased twofold, resulting in a decreased
lifespan of 7 to 10 years (",
" <a class=\"graphic graphic_figure graphicRef72445 \" href=\"UTD.htm?
25/41/26270\">",
" figure 1",
" </a>",
" ) [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/29\">",
" 29",
" </a>",
" ]. Other studies have shown that RA patients have a 50 percent increased risk
of premature mortality and that their life expectancy is decreased by 3 to 10 years
[",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/40\">",
" 40",
" </a>",
" ]. Mortality directly due to RA itself was low (9.8 percent of the deaths),
although precise causes were not reported.",
" </p>",
" <p>",
" This marked increase in mortality may reflect referral bias as many of these
patients were being treated in large tertiary care centers. In a community-based
study of 450 adult patients with RA, for example, the increased death rate was
somewhat less than that observed in large medical centers [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/41\">",
" 41",
" </a>",
" ]. The ratio of observed to expected deaths (standardized mortality ratio
[SMR]) was 1.38 overall, with women bearing the highest risk (SMR of 1.55 and 1.07
for women and men, respectively). Additional data on this almost exclusively white
North American population confirmed a modest age and gender adjusted increase in
SMR of 1.27 (95% CI 1.13-1.41) and no significant change in the risk of premature
death during the 40-year period of observation [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/42\">",
" 42",
" </a>",
" ].",
" </p>",
" <p>",
" Two meta-analyses addressing cardiovascular mortality have largely confirmed
these results, with SMRs of around 1.5, suggesting a 50 to 60 percent increased
risk of mortality from cardiovascular disease [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/43,44\">",
" 43,44",
" </a>",
" ]. One of these studies [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/44\">",
" 44",
" </a>",
" ] showed no change in SMR over a 50-year period. Thus, improvements in therapy
have not yet been accompanied by improvements in survival in relation to the
general population; moreover, there has been a widening gap between mortality rates
in patients with RA and the improving mortality rate in the general population [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/40\">",
" 40",
" </a>",
" ]. Furthermore, there is an excess risk of 50 to 60 percent of cardiovascular
mortality in patients with RA that has not decreased [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/40\">",
" 40",
" </a>",
" ]. Importantly, these studies also emphasize that assessment of cardiovascular
risk should be part of the routine long-term management of patients with RA.",
" </p>",
" <p>",
" Mechanisms by which premature mortality can occur in RA include cardiac
disease, amyloidosis, transection of the cord due to cervical spine instability,
and respiratory failure due to fibrosing alveolitis. Much more common causes of
death were related to comorbid illnesses, particularly cardiovascular and
cerebrovascular disease, infection, lymphomas, and gastrointestinal bleeding. With
regard to deaths due to acute myocardial infarction, lower rates have been noted in
more recently diagnosed and treated cohorts [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/45\">",
" 45",
" </a>",
" ]. Patients with RA with a first cardiovascular event appear to have a higher
mortality rate during the subsequent 30 days than those without RA [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/46\">",
" 46",
" </a>",
" ]. The reason for the difference in fatalities (18 versus 11 percent,
respectively) is uncertain. Possible explanations include a greater prevalence of
severe epicardial coronary artery disease in patients with RA who present with new
ischemic symptoms [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/47\">",
" 47",
" </a>",
" ] or the presence of small vessel disease that is not amenable to angioplasty
or bypass surgery [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/48\">",
" 48",
" </a>",
" ].",
" </p>",
" <p>",
" Some studies have found a decrease or at least no increase in the expected
number of deaths from cancer, probably reflecting the increase from other causes
[",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/49\">",
" 49",
" </a>",
" ]. However, one large study of over 20,000 patients with RA reported an
increased incidence of death resulting from lung cancer [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/50\">",
" 50",
" </a>",
" ].",
" </p>",
" <p>",
" Patients who respond to therapy, particularly a disease modifying rheumatic
drug, may have lower mortality. As an example, one long-term prospective study of
271 patients begun on MTX found that the group with more than 50 percent
improvement had a SMR of 1.47 [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/51\">",
" 51",
" </a>",
" ]; by comparison, the SMRs of patients who had no improvement or who had
discontinued treatment were 4.11 and 5.56, respectively.",
" </p>",
" <p>",
" However a beneficial effect of MTX may or may not be confined to those who
have a good response. In a cohort study of 1240 patients with RA at one clinical
center in North America, 191 patients died [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/52\">",
" 52",
" </a>",
" ]. MTX was prescribed for 588 patients; treatment decisions were not made in a
randomized fashion. The group that received MTX had poorer prognostic indicators
and more frequent",
" <a class=\"drug drug_general\" href=\"UTD.htm?37/43/38585?source=see_link\">",
" prednisone",
" </a>",
" use than the MTX-naive group (37 versus 22 percent, respectively).
Approximately 70 percent of both groups were women, and the average age was 57
years.",
" </p>",
" <p>",
" After adjustment for possible confounding factors including age, sex, marital
status, disease duration, body mass index, disability score, blood pressure,
presence of absence of diabetes, and use of cholesterol lowering drugs, the hazard
ratio for all cause mortality among MTX-treated patients was 0.4 (95% CI 0.2-
0.8).",
" </p>",
" <p>",
" When deaths were divided into those due to cardiovascular disease and those
due to other causes, the hazard ratios were 0.3 and 0.6, respectively. The
reduction in cardiovascular risk was statistically significant, while that of non-
cardiovascular mortality was not. The patients in this study were treated beginning
in the 1980s and 1990s, prior to the general availability of anticytokine therapy.
Use of traditional disease modifying antirheumatic drugs (DMARDs) other than MTX
did not appear to have a similar survival advantage (hazard ratio 1.0).",
" </p>",
" <p>",
" Independent predictors of mortality include age, education, male sex,
function, rheumatoid factor, nodules, erythrocyte sedimentation rate, CRP, elevated
DAS28 score, anti-CCP, joint count, and NSAID and",
" <a class=\"drug drug_general\" href=\"UTD.htm?37/43/38585?source=see_link\">",
" prednisone",
" </a>",
" use, all markers of clinical severity [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/29,40,53-55\">",
" 29,40,53-55",
" </a>",
" ]. A lower than ideal body weight (as indicated by a body mass index
calculated as weight in kilograms divided by the height in meters squared that is
&lt;20) may be associated with increased mortality rate [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/56\">",
" 56",
" </a>",
" ]. Other factors that may contribute to reduced longevity include the presence
of extraarticular disease, depression [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/57\">",
" 57",
" </a>",
" ], circulating immune complexes [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/37\">",
" 37",
" </a>",
" ], increased levels of soluble tumor necrosis factor receptors [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/58\">",
" 58",
" </a>",
" ], and the presence of certain HLA DRB1 alleles (",
" <a class=\"graphic graphic_figure graphicRef72445 \" href=\"UTD.htm?
25/41/26270\">",
" figure 1",
" </a>",
" ) [",
" <a class=\"abstract\" href=\"UTD.htm?0/11/184/abstract/59\">",
" 59",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?22/63/23546?
source=see_link\">",
" \"HLA and other susceptibility genes in rheumatoid arthritis\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"PATIENT_INFORMATION\">",
" <span class=\"h1\">",
" INFORMATION FOR PATIENTS",
" </span>",
" &nbsp;&mdash;&nbsp;UpToDate offers two types of patient education materials,
&ldquo;The Basics&rdquo; and &ldquo;Beyond the Basics.&rdquo; The Basics patient
education pieces are written in plain language, at the 5",
" <sup>",
" th",
" </sup>",
" to 6",
" <sup>",
" th",
" </sup>",
" grade reading level, and they answer the four or five key questions a patient
might have about a given condition. These articles are best for patients who want a
general overview and who prefer short, easy-to-read materials. Beyond the Basics
patient education pieces are longer, more sophisticated, and more detailed. These
articles are written at the 10",
" <sup>",
" th",
" </sup>",
" to 12",
" <sup>",
" th",
" </sup>",
" grade reading level and are best for patients who want in-depth information
and are comfortable with some medical jargon.",
" </p>",
" <p>",
" Here are the patient education articles that are relevant to this topic. We
encourage you to print or e-mail these topics to your patients. (You can also
locate patient education articles on a variety of subjects by searching on
&ldquo;patient info&rdquo; and the keyword(s) of interest.)",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Beyond the Basics topics (see",
" <a class=\"medical medical_patient\" href=\"UTD.htm?20/61/21463?
source=see_link\">",
" \"Patient information: Rheumatoid arthritis symptoms and diagnosis (Beyond
the Basics)\"",
" </a>",
" and",
" <a class=\"medical medical_patient\" href=\"UTD.htm?23/44/24264?
source=see_link\">",
" \"Patient information: Rheumatoid arthritis treatment (Beyond the
Basics)\"",
" </a>",
" and",
" <a class=\"medical medical_patient\" href=\"UTD.htm?38/29/39378?
source=see_link\">",
" \"Patient information: Complementary therapies for rheumatoid arthritis
(Beyond the Basics)\"",
" </a>",
" )",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H361188233\">",
" <span class=\"h1\">",
" SUMMARY",
" </span>",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" The outcome of rheumatoid arthritis (RA) is dependent upon the degree of
disease activity, joint damage, the physical functional status of the patient,
psychological health, and the presence of comorbid illness. (See",
" <a class=\"local\" href=\"#H1\">",
" 'Introduction'",
" </a>",
" above.)",
" </li>",
" <li>",
" Loss of functional capacity in RA is a result of the summation of loss of
function in individual joints, which depends upon numerous factors. Since
functional capacity is an important determinant of the natural history of RA and is
a useful tool for assessing the effectiveness of therapeutic interventions, many
instruments for patient evaluation have been developed. (See",
" <a class=\"local\" href=\"#H2\">",
" 'Functional capacity'",
" </a>",
" above and",
" <a class=\"local\" href=\"#H3\">",
" 'Assessment'",
" </a>",
" above.)",
" </li>",
" <li>",
" The long-term functional outlook is variable for patients who present early
in the course of their illness and are treated. The combination of inflammation and
joint damage leads to functional impairment. The impact of RA on the ability to
earn a living is uncertain. (See",
" <a class=\"local\" href=\"#H5\">",
" 'Long-term outcomes'",
" </a>",
" above and",
" <a class=\"local\" href=\"#H4\">",
" 'Disability due to RA'",
" </a>",
" above and",
" <a class=\"local\" href=\"#H6\">",
" 'Impact on employment'",
" </a>",
" above.)",
" </li>",
" <li>",
" Patients with RA have an increased prevalence of other serious illnesses.
The predominant conditions contributing to the comorbidity and mortality of RA are
(",
" <a class=\"graphic graphic_table graphicRef82537 \" href=\"UTD.htm?
26/45/27355\">",
" table 1",
" </a>",
" ) (see",
" <a class=\"local\" href=\"#H7\">",
" 'Comorbidity and mortality'",
" </a>",
" above):",
" </li>",
" </ul>",
" </p>",
" <p>",
" <ul class=\"hyphen-block\">",
" <li>",
" Infections, particularly pulmonary, skin, and joint infections, which occur
with increased frequency in RA (see",
" <a class=\"local\" href=\"#H8\">",
" 'Infection'",
" </a>",
" above)",
" </li>",
" <li>",
" Renal impairment, which is uncommon but may be due to RA itself or to drug
therapy (see",
" <a class=\"local\" href=\"#H9\">",
" 'Renal disease'",
" </a>",
" above)",
" </li>",
" <li>",
" Lymphoproliferative disorders, including lymphoma, which occur with
increased frequency in patients with RA (see",
" <a class=\"local\" href=\"#H10\">",
" 'Lymphoproliferative disorders'",
" </a>",
" above)",
" </li>",
" <li>",
" Cardiovascular disease, which appears to correlate with the activity and
duration of the RA (see",
" <a class=\"local\" href=\"#H11\">",
" 'Cardiovascular disease'",
" </a>",
" above)",
" </li>",
" </ul>",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" RA patients have an increased risk of premature mortality, and their life
expectancy is decreased, although most of the mortality is not due directly to RA
itself. (See",
" <a class=\"local\" href=\"#H12\">",
" 'Mortality'",
" </a>",
" above.)",
" </li>",
" </ul>",
" </p>",
" </div>",
" <div id=\"topicAgreement\">",
" Use of UpToDate is subject to the",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
target=\"_blank\">",
" Subscription and License Agreement",
" </a>",
" .",
" </div>",
" <div class=\"headingAnchor\" id=\"references\">",
" <h1>",
" REFERENCES",
" </h1>",
" <ol id=\"reference\">",
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" Krishnan E, Lingala VB, Singh G. Declines in mortality from acute myocardial
infarction in successive incidence and birth cohorts of patients with rheumatoid
arthritis. Circulation 2004; 110:1774.",
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rates following a first acute cardiovascular event in patients with rheumatoid
arthritis. Arthritis Rheum 2006; 54:2061.",
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independent risk factor for multi-vessel coronary artery disease: a case control
study. Arthritis Res Ther 2005; 7:R984.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?0/11/184/abstract/48\">",
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patient with rheumatoid arthritis. J Rheumatol 2005; 32:754.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?0/11/184/abstract/49\">",
" van den Borne BE, Landew&eacute; RB, Houkes I, et al. No increased risk of
malignancies and mortality in cyclosporin A-treated patients with rheumatoid
arthritis. Arthritis Rheum 1998; 41:1930.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/11/184/abstract/50\">",
" Mellemkjaer L, Linet MS, Gridley G, et al. Rheumatoid arthritis and cancer
risk. Eur J Cancer 1996; 32A:1753.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/11/184/abstract/51\">",
" Krause D, Schleusser B, Herborn G, Rau R. Response to methotrexate treatment
is associated with reduced mortality in patients with severe rheumatoid arthritis.
Arthritis Rheum 2000; 43:14.",
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" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/11/184/abstract/52\">",
" Choi HK, Hern&aacute;n MA, Seeger JD, et al. Methotrexate and mortality in
patients with rheumatoid arthritis: a prospective study. Lancet 2002; 359:1173.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/11/184/abstract/53\">",
" Myllykangas-Luosuj&auml;rvi R, Aho K, Isom&auml;ki H. Death attributed to
antirheumatic medication in a nationwide series of 1666 patients with rheumatoid
arthritis who have died. J Rheumatol 1995; 22:2214.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/11/184/abstract/54\">",
" Wolfe F, Michaud K, Gefeller O, Choi HK. Predicting mortality in patients
with rheumatoid arthritis. Arthritis Rheum 2003; 48:1530.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/11/184/abstract/55\">",
" Gonzalez A, Icen M, Kremers HM, et al. Mortality trends in rheumatoid
arthritis: the role of rheumatoid factor. J Rheumatol 2008; 35:1009.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/11/184/abstract/56\">",
" Escalante A, Haas RW, del Rinc&oacute;n I. Paradoxical effect of body mass
index on survival in rheumatoid arthritis: role of comorbidity and systemic
inflammation. Arch Intern Med 2005; 165:1624.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/11/184/abstract/57\">",
" Ang DC, Choi H, Kroenke K, Wolfe F. Comorbid depression is an independent
risk factor for mortality in patients with rheumatoid arthritis. J Rheumatol 2005;
32:1013.",
" </a>",
" </li>",
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" Mattey DL, Glossop JR, Nixon NB, Dawes PT. Circulating levels of tumor
necrosis factor receptors are highly predictive of mortality in patients with
rheumatoid arthritis. Arthritis Rheum 2007; 56:3940.",
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" Mattey DL, Thomson W, Ollier WE, et al. Association of DRB1 shared epitope
genotypes with early mortality in rheumatoid arthritis: results of eighteen years
of followup from the early rheumatoid arthritis study. Arthritis Rheum 2007;
56:1408.",
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" </div>",
" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Courtesy of Cristina Magi-Galluzzi, MD, PhD.",
" </div>",
" </div>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 470px\">",
" <div class=\"ttl\">",
" Urothelial carcinoma in situ (CIS)",
" </div>",
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" </div>",
" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Courtesy of Cristina Magi-Galluzzi, MD, PhD.",
" </div>",
" </div>",
" </div>",
" </div>",
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var outline_f0_11_185=null;
var title_f0_11_186="Cerebral vascular territories";
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" &copy;2013 UpToDate",
" <sup>",
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" <div class=\"ttl\">",
" Major cerebral vascular territories",
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" </div>",
" <div class=\"lgnd\">",
" Representation of the territories of the major cerebral vessels shown in a
coronal section of the brain.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Reproduced with permission from Kistler, JP, et al, Cerebrovascular Diseases.
Harrison's Principles of Internal Medicine, 13th ed, McGraw-Hill, New York 1994.
Copyright 1994 McGraw-Hill Companies, Inc.",
" </div>",
" </div>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 555px\">",
" <div class=\"ttl\">",
" Anterior cerebral artery distribution and signs and symptoms of occlusion",
" </div>",
" <div class=\"cntnt\" style=\"width: 535px; height: 578px; background-image:
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" </div>",
" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Reproduced with permission from Kistler, JP, et al, Cerebrovascular Diseases,
Harrison's Principles of Internal Medicine, 13th ed. McGraw-Hill, New York 1994.
Copyright 1994 McGraw-Hill Companies, Inc.",
" </div>",
" </div>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 601px\">",
" <div class=\"ttl\">",
" Middle cerebral artery distribution and signs and symptoms of occlusion",
" </div>",
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