wikidoc - User contributions [en]

User:Sergekorjian

2018-02-05T01:16:27Z

Sergekorjian:

__NOTOC__
==Serge Korjian==
[[Image:SergeKorjianMD.jpg|right|thumb|200px]]
'''Serge Korjian, MD''' 
Email: [mailto:serge.korjian@wikidoc.org serge.korjian@wikidoc.org] 

==Current Position==
Senior Deputy Editor-in-Chief, ''WikiDoc.org'' 
Director of the WikiDoc CME Project 
Postdoctoral research fellow, PERFUSE Study Group

==Professional Background==
Dr. Serge Korjian is a postdoctoral research fellow of cardiovascular medicine at the PERFUSE Study Group at Beth Israel Deaconess Medical Center. He received his M.D. from the Lebanese American University in Beirut, after which he joined PERFUSE. Dr. Korjian is a senior deputy editor-in-chief at ''WikiDoc.org'' where he authors and oversees the editing of several topics in cardiology, nephrology, infectious disease, and gastroenterology. He has also contributed approximately 300 high-quality USMLE Step 1 style questions for the Wiki Board Review Project. Dr. Korjian is also the director of the WikiDoc CME Initiative that aims to provide CME credit to all physicians who use WikiDoc.

==Education==
Lebanese American University, Gilbert and Rose-Mary Chagoury School of Medicine ''Class of 2014''

Template:WikiDoc tools2

2016-05-31T13:01:54Z

Sergekorjian: /* How to Create A Page */

__NOTOC__
{| width="100%" cellpadding="2" cellspacing="5" style="vertical-align:top; background:#F9F9F9;"
|-
! style="margin:0; background:#cedff2; font-size:120%; font-weight:bold; border:1px solid#a3b0bf; text-align:left; color:#000; padding:0.2em 0.4em; " colspan="2" | Tools to Edit WikiDoc
|-
| style="color:#000; font-size:100%; width: 50%; vertical-align: top;" |

==List of Projects==
* [[Board review project|Board Review Project]]
* [[Critical pathways project|Critical Pathways Project]]
* [[Crowdiagnosis|Crowdiagnosis Project]]
* [[Dermatology atlas project|Dermatology Atlas Project]]
* [[Differential diagnosis project|Differential Diagnosis Project]]
* [[Drug project|Drug Project]]
* [[Genetic disorder project|Genetic Disorder Project]]
* [[Guidelines project|Guidelines Project]]
* [[Incidence and Prevalence Project|Incidence and Prevalence Project]]
* [[Infectious Disease Project|Infectious Disease Project]]
* [[Microchapters project|Microchapters Project]]
* [[Oncology Project|Oncology and Mass Project]]
* [[Resident survival guide project|Resident Survival Guide Project]]
* [[WikiDoc in languages other than English|WikiDoc in Other Languages]]
* [[WikiPatient|WikiPatient]]

==Quick Start==

* [[Get Started Here|Get Started Here]]
* [[Getting started video|Getting Started Video]]
* [[Policies & Guidelines|Review Policies and Guidelines]]
* [[How to login|How to Login]]
* [[Searching|How to Search Pages]]
* [[Creating pages|How to Start a New Page]]
* [[How to edit a page|How to Edit a Page]]
* [[How to create a user page|How to Create Your User Page]]
* [[Cheat Sheet|Cheat Sheet: A quick reference you can print out]]
* [[Quick Guidelines for Editing]]

==How to Create A Page==
{{fontcolor|#FF0000| Before creating/editing a topic, always search for its synonyms (read instructions [[Synonyms and keywords template#Where Do I Find Synonyms?|{{fontcolor|#000000|here}}]] before operating).}}
* [[Microchapters template|Template to Add a New Microchaptered Disease Page]]
* [[WikiDoc disease template|Template to Add the Navigational Structure on Right Hand Side]]
* [[Template to add a new disease abbreviated|Template to Add an Abbreviated New Disease Page]]
* [[Patient information page|How to Create a WikiPatient Page]]
* [[Patient information page template|Template to Add a New Patient Page]]
* [[Board review project|How to Create a WikiDoc Board Review Question]]
* [[Resident survival guide project|Template to Add a Resident Survival Guide Page]]

==How to Edit A Page==
{{fontcolor|#FF0000| Before creating/editing a topic, always search for its synonyms (read instructions [[Synonyms and keywords template#Where Do I Find Synonyms?|{{fontcolor|#000000|here}}]] before operating).}}
* [[How to create an algorithm|Algorithms]]
* [[Basic formatting|Basic Formatting]]
* [[Lists|Bullet Points]]
* [[Web colors|Colors]]
* [[Columns|Columns]]
* [[Converting word documents to wiki text|Converting Word Documents to Wiki Text]]
* [[Copyleft sources|Copyleft Sources]]
* [[Categories]]
* [[Insert dates and times|Dates and Times]]
* [[Ignoring Formatting|Ignoring Formatting]]
* [[Images|Image and Picture Insertion]]
* [[Links|Links to other WikiDoc Pages & to External Sites]]
* [[Moving pages|Moving Pages]]
* [[Images|Picture and Image Insertion]]
* [[Redirection|Redirects: When Multiple Topics Should Go To The Same Page (MI, Acute MI, AMI)]]
* [[References|References]]
* [[Slides|Slidesets for download]]
* [[Audios|Sound or audio file insertion]]
* [[Inserting Statistics|Statistics]]
* [[SVG Images]]
* [[Tables|Tables]]
* [[Editing the Table of Contents|Table of Contents]]
* [[Templates|Templates]]
* [[Tracking changes|Tracking Changes You Have Made]]
* [[Videos|Videos]]
* [[Tracking changes#Watchlist|Watch a page & receive automated alerts about changes]]

| style="color:#000; font-size: 100%; width: 50%; vertical-align: top;" |

==How to Edit Specific Page Types==
* [[Template for creating a single page chapter|How to Create a Single Page Chapter (Coding + Templates Included)]]
* [[Guide to Creating a Disease Page|Overview of How To Edit Specific Pages]]
* [[Patient information page template|Patient Information]]
* [[Synonyms and keywords template|Synonyms and Keywords]]
* [[Overview template|Overview]]
* [[Historical perspective template|Historical Perspective]]
* [[Classification template|Classification + Staging]]
* [[Pathophysiology template|Pathophysiology]]
* [[Crowdiagnosis project template|Causes]]
* [[Microbiology template|Causes (Microbiology)]]
* [[Differentiating (disease name) from other diseases page|Differentiating (disease name) From Other Diseases]]
* [[Epidemiology and demographics template|Epidemiology and Demographics]]
* [[Risk factor template|Risk Factors]]
* [[Screening template|Screening]]
* [[Natural history, complications and prognosis template|Natural History, Complications, Prognosis]]
* [[Diagnostic criteria template|Diagnostic Criteria]]
* [[History and symptoms template|History and Symptoms]]
* [[Physical examination template|Physical Examination]]
* [[Laboratory findings template|Laboratory Findings]]
* [[Electrocardiogram template|Electrocardiogram]]
* [[Chest x ray template|Chest X Ray]]
* [[CT template|CT Scan / MRI]]
* [[Echocardiography or ultrasound template|Echocardiography or Ultrasound]]
* [[Other imaging findings template|Other Imaging Findings]]
* [[Biopsy template|Biopsy]]
* [[Medical therapy template|Medical Therapy]]
* [[Surgery template|Surgery]]
* [[Prevention template|Prevention]]
* [[Cost Effectiveness of Therapy|Cost Effectiveness]]
* [[Case Studies]]

==Upload and Import Files==

* [[Special:Upload|Upload an Image or Powerpoint Slide]]

==Manual of Style==

* [[Guide to medical syntax|WikiDoc Writing Style]]
* [[Capitalization|Capitalization]]
* [[Fellows workbook#Feedback from CMG|Common Editing Errors]]

==Site Administrator Tools==

* [[Special:SpecialPages|Special Pages]]
* [[Special:BrokenRedirects|Double Redirect Pages That Need to be Fixed]]

|}

Template to add a new disease abbreviated

2016-05-31T13:00:34Z

Sergekorjian:

__NOTOC__
{{SI}}

'''For patient information, click Disease Name (patient information)'''

{{CMG}}

'''''Synonyms and keywords:'''''

== Overview ==

==Historical Perspective==

==Classification==

==Pathophysiology==

=== Genetics ===

===Associated Conditions===

==Causes==
===Life Threatening Causes===

===Common Causes===

===Causes by Organ System===

{|style="width:80%; height:100px" border="1"
|style="height:100px"; style="width:25%" border="1" bgcolor="LightSteelBlue" |'''Cardiovascular'''
|style="height:100px"; style="width:75%" border="1" bgcolor="Beige" | No underlying causes
|-
|bgcolor="LightSteelBlue"| '''Chemical/Poisoning'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Dental'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Dermatologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Drug Side Effect'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Ear Nose Throat'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Endocrine'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Environmental'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Gastroenterologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Genetic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Hematologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Iatrogenic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Infectious Disease'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Musculoskeletal/Orthopedic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Neurologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Nutritional/Metabolic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Obstetric/Gynecologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Oncologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Ophthalmologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Overdose/Toxicity'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Psychiatric'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Pulmonary'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Renal/Electrolyte'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Rheumatology/Immunology/Allergy'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Sexual'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Trauma'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Urologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Miscellaneous'''
|bgcolor="Beige"| No underlying causes
|-
|}

===Causes in Alphabetical Order===
: List the causes of the disease in alphabetical order. You may need to list across the page, as seen [[Jaundice causes#Causes in Alphabetical Order|here]]
{{col-begin|width=80%}}
{{col-break|width=33%}}
* Disease A

{{col-break|width=33%}}
* Disease B

{{col-break|width=33%}}
* Disease C
{{col-end}}

==Differentiating type page name here from other Diseases==

== Epidemiology and Demographics ==

== Risk Factors ==

== Screening ==

== Natural History, Complications, and Prognosis==

== Diagnosis ==

=== Symptoms ===

===Family History===

=== Physical Examination ===

==== Appearance of the Patient ====

====Vital Signs====

====Skin====

====Head====

==== Eyes ====

==== Ear ====

====Nose====

====Throat ====

==== Heart ====

==== Lungs ====

==== Abdomen ====

==== Extremities ====

==== Neurologic ====

==== Other ====

=== Laboratory Findings ===

==== Biomarker Studies ====

====CT ====

==== MRI ====

==== Ultrasound ====

== Treatment ==
=== Pharmacotherapy ===

==== Acute Pharmacotherapies ====

==== Chronic Pharmacotherapies ====

=== Surgery and Device Based Therapy ===

==== Indications for Surgery ====

==== Pre-Operative Assessment ====

==== Post-Operative Management ====

===Primary Prevention===
====Genetic Counseling====

==References==
{{reflist|2}}

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

[[Category:Disease]]
[[Category:FLK]]

Template to add a new disease abbreviated

2016-05-31T12:59:51Z

Sergekorjian:

__NOTOC__
{{SI}}

'''For patient information, click [[Hypoventilation (patient information)|Hypoventilation]]'''

{{CMG}}

'''''Synonyms and keywords:'''''

== Overview ==

==Historical Perspective==

==Classification==

==Pathophysiology==

=== Genetics ===

===Associated Conditions===

==Causes==
===Life Threatening Causes===

===Common Causes===

===Causes by Organ System===

{|style="width:80%; height:100px" border="1"
|style="height:100px"; style="width:25%" border="1" bgcolor="LightSteelBlue" |'''Cardiovascular'''
|style="height:100px"; style="width:75%" border="1" bgcolor="Beige" | No underlying causes
|-
|bgcolor="LightSteelBlue"| '''Chemical/Poisoning'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Dental'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Dermatologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Drug Side Effect'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Ear Nose Throat'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Endocrine'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Environmental'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Gastroenterologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Genetic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Hematologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Iatrogenic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Infectious Disease'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Musculoskeletal/Orthopedic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Neurologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Nutritional/Metabolic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Obstetric/Gynecologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Oncologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Ophthalmologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Overdose/Toxicity'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Psychiatric'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Pulmonary'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Renal/Electrolyte'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Rheumatology/Immunology/Allergy'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Sexual'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Trauma'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Urologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Miscellaneous'''
|bgcolor="Beige"| No underlying causes
|-
|}

===Causes in Alphabetical Order===
: List the causes of the disease in alphabetical order. You may need to list across the page, as seen [[Jaundice causes#Causes in Alphabetical Order|here]]
{{col-begin|width=80%}}
{{col-break|width=33%}}
* Disease A

{{col-break|width=33%}}
* Disease B

{{col-break|width=33%}}
* Disease C
{{col-end}}

==Differentiating type page name here from other Diseases==

== Epidemiology and Demographics ==

== Risk Factors ==

== Screening ==

== Natural History, Complications, and Prognosis==

== Diagnosis ==

=== Symptoms ===

===Family History===

=== Physical Examination ===

==== Appearance of the Patient ====

====Vital Signs====

====Skin====

====Head====

==== Eyes ====

==== Ear ====

====Nose====

====Throat ====

==== Heart ====

==== Lungs ====

==== Abdomen ====

==== Extremities ====

==== Neurologic ====

==== Other ====

=== Laboratory Findings ===

==== Biomarker Studies ====

====CT ====

==== MRI ====

==== Ultrasound ====

== Treatment ==
=== Pharmacotherapy ===

==== Acute Pharmacotherapies ====

==== Chronic Pharmacotherapies ====

=== Surgery and Device Based Therapy ===

==== Indications for Surgery ====

==== Pre-Operative Assessment ====

==== Post-Operative Management ====

===Primary Prevention===
====Genetic Counseling====

==References==
{{reflist|2}}

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

[[Category:Disease]]
[[Category:FLK]]

Template:WikiDoc tools2

2016-05-31T12:59:17Z

Sergekorjian: /* How to Create A Page */

__NOTOC__
{| width="100%" cellpadding="2" cellspacing="5" style="vertical-align:top; background:#F9F9F9;"
|-
! style="margin:0; background:#cedff2; font-size:120%; font-weight:bold; border:1px solid#a3b0bf; text-align:left; color:#000; padding:0.2em 0.4em; " colspan="2" | Tools to Edit WikiDoc
|-
| style="color:#000; font-size:100%; width: 50%; vertical-align: top;" |

==List of Projects==
* [[Board review project|Board Review Project]]
* [[Critical pathways project|Critical Pathways Project]]
* [[Crowdiagnosis|Crowdiagnosis Project]]
* [[Dermatology atlas project|Dermatology Atlas Project]]
* [[Differential diagnosis project|Differential Diagnosis Project]]
* [[Drug project|Drug Project]]
* [[Genetic disorder project|Genetic Disorder Project]]
* [[Guidelines project|Guidelines Project]]
* [[Incidence and Prevalence Project|Incidence and Prevalence Project]]
* [[Infectious Disease Project|Infectious Disease Project]]
* [[Microchapters project|Microchapters Project]]
* [[Oncology Project|Oncology and Mass Project]]
* [[Resident survival guide project|Resident Survival Guide Project]]
* [[WikiDoc in languages other than English|WikiDoc in Other Languages]]
* [[WikiPatient|WikiPatient]]

==Quick Start==

* [[Get Started Here|Get Started Here]]
* [[Getting started video|Getting Started Video]]
* [[Policies & Guidelines|Review Policies and Guidelines]]
* [[How to login|How to Login]]
* [[Searching|How to Search Pages]]
* [[Creating pages|How to Start a New Page]]
* [[How to edit a page|How to Edit a Page]]
* [[How to create a user page|How to Create Your User Page]]
* [[Cheat Sheet|Cheat Sheet: A quick reference you can print out]]
* [[Quick Guidelines for Editing]]

==How to Create A Page==
{{fontcolor|#FF0000| Before creating/editing a topic, always search for its synonyms (read instructions [[Synonyms and keywords template#Where Do I Find Synonyms?|{{fontcolor|#000000|here}}]] before operating).}}
* [[Template to add a new disease abbreviated|Template to Add an Abbreviated New Disease Page]]
* [[WikiDoc disease template|Template to Add the Navigational Structure on Right Hand Side]]
* [[Patient information page|How to Create a WikiPatient Page]]
* [[Patient information page template|Template to Add a New Patient Page]]
* [[Board review project|How to Create a WikiDoc Board Review Question]]
* [[Resident survival guide project|Template to Add a Resident Survival Guide Page]]

==How to Edit A Page==
{{fontcolor|#FF0000| Before creating/editing a topic, always search for its synonyms (read instructions [[Synonyms and keywords template#Where Do I Find Synonyms?|{{fontcolor|#000000|here}}]] before operating).}}
* [[How to create an algorithm|Algorithms]]
* [[Basic formatting|Basic Formatting]]
* [[Lists|Bullet Points]]
* [[Web colors|Colors]]
* [[Columns|Columns]]
* [[Converting word documents to wiki text|Converting Word Documents to Wiki Text]]
* [[Copyleft sources|Copyleft Sources]]
* [[Categories]]
* [[Insert dates and times|Dates and Times]]
* [[Ignoring Formatting|Ignoring Formatting]]
* [[Images|Image and Picture Insertion]]
* [[Links|Links to other WikiDoc Pages & to External Sites]]
* [[Moving pages|Moving Pages]]
* [[Images|Picture and Image Insertion]]
* [[Redirection|Redirects: When Multiple Topics Should Go To The Same Page (MI, Acute MI, AMI)]]
* [[References|References]]
* [[Slides|Slidesets for download]]
* [[Audios|Sound or audio file insertion]]
* [[Inserting Statistics|Statistics]]
* [[SVG Images]]
* [[Tables|Tables]]
* [[Editing the Table of Contents|Table of Contents]]
* [[Templates|Templates]]
* [[Tracking changes|Tracking Changes You Have Made]]
* [[Videos|Videos]]
* [[Tracking changes#Watchlist|Watch a page & receive automated alerts about changes]]

| style="color:#000; font-size: 100%; width: 50%; vertical-align: top;" |

==How to Edit Specific Page Types==
* [[Template for creating a single page chapter|How to Create a Single Page Chapter (Coding + Templates Included)]]
* [[Guide to Creating a Disease Page|Overview of How To Edit Specific Pages]]
* [[Patient information page template|Patient Information]]
* [[Synonyms and keywords template|Synonyms and Keywords]]
* [[Overview template|Overview]]
* [[Historical perspective template|Historical Perspective]]
* [[Classification template|Classification + Staging]]
* [[Pathophysiology template|Pathophysiology]]
* [[Crowdiagnosis project template|Causes]]
* [[Microbiology template|Causes (Microbiology)]]
* [[Differentiating (disease name) from other diseases page|Differentiating (disease name) From Other Diseases]]
* [[Epidemiology and demographics template|Epidemiology and Demographics]]
* [[Risk factor template|Risk Factors]]
* [[Screening template|Screening]]
* [[Natural history, complications and prognosis template|Natural History, Complications, Prognosis]]
* [[Diagnostic criteria template|Diagnostic Criteria]]
* [[History and symptoms template|History and Symptoms]]
* [[Physical examination template|Physical Examination]]
* [[Laboratory findings template|Laboratory Findings]]
* [[Electrocardiogram template|Electrocardiogram]]
* [[Chest x ray template|Chest X Ray]]
* [[CT template|CT Scan / MRI]]
* [[Echocardiography or ultrasound template|Echocardiography or Ultrasound]]
* [[Other imaging findings template|Other Imaging Findings]]
* [[Biopsy template|Biopsy]]
* [[Medical therapy template|Medical Therapy]]
* [[Surgery template|Surgery]]
* [[Prevention template|Prevention]]
* [[Cost Effectiveness of Therapy|Cost Effectiveness]]
* [[Case Studies]]

==Upload and Import Files==

* [[Special:Upload|Upload an Image or Powerpoint Slide]]

==Manual of Style==

* [[Guide to medical syntax|WikiDoc Writing Style]]
* [[Capitalization|Capitalization]]
* [[Fellows workbook#Feedback from CMG|Common Editing Errors]]

==Site Administrator Tools==

* [[Special:SpecialPages|Special Pages]]
* [[Special:BrokenRedirects|Double Redirect Pages That Need to be Fixed]]

|}

West nile virus

2016-05-04T14:24:45Z

Sergekorjian:

__NOTOC__
{{West nile virus infection}}

{{About0|West nile virus infection}}

{{CMG}}

==Overview==
WNV is an enveloped positive-sense ssRNA virus of 11000 base pairs (bp) that is considered a member of the Japanese encephalitis serocomplex. It belongs to the genus Flavivirus and family Flaviviridae. Its RNA encodes structural and non-structural proteins. Although 7 lineages of WNV have been described, only lineage 1 and 2 are clinically significant. The viral natural reservoir includes many species, such as humans, horses, dogs, and cats; but the main natural reservoir is birds.

==Taxonomy==
Viruses; ssRNA viruses; ssRNA positive-strand viruses, no DNA stage; Flaviviridae; Flavivirus; Japanese encephalitis virus group<ref name=NCBI>{{cite web | title = West Nile Virus | url = http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=11082&lvl=3&lin=f&keep=1&srchmode=1&unlock }}</ref>

==Biology==

{| style="float: right;"
| [[File:WNV2.jpg|200px|thumb|none| Presence of West Nile virus virions, in an isolate that was grown in a cell culture. ''Image provided by the CDC [http://phil.cdc.gov/phil/details.asp Centers for Disease Control and Prevention] ''<ref>{{Cite web | title = http://phil.cdc.gov/phil/details.asp | url = http://phil.cdc.gov/phil/details.asp}}</ref>]]
|}
WNV is a member of Japanese encephalitis serocomplex and belongs to the [[genus]] [[Flavivirus]], family [[Flaviviridae]]. Other [[species]] of the this serocomplex include the [[St Louis encephalitis virus]] and the [[Japanese encephalitis virus]].<ref name="pmid23860989">{{cite journal| author=Petersen LR, Brault AC, Nasci RS| title=West Nile virus: review of the literature. | journal=JAMA | year= 2013 | volume= 310 | issue= 3 | pages= 308-15 | pmid=23860989 | doi=10.1001/jama.2013.8042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23860989 }} </ref>

The WNV has an icosahedral symmetry, with a smooth surface.<ref name="Mukhopadhyay2003">{{cite journal|last1=Mukhopadhyay|first1=S.|title=Structure of West Nile Virus|journal=Science|volume=302|issue=5643|year=2003|pages=248–248|issn=0036-8075|doi=10.1126/science.1089316}}</ref> It is an enveloped virus with a nucleocapsid core built of [[RNA]] and [[capsid]] proteins. Its [[genome]] is contained in a single-stranded [[RNA]] of about 11000 bp.<ref name="CampbellMarfin2002">{{cite journal|last1=Campbell|first1=Grant L|last2=Marfin|first2=Anthony A|last3=Lanciotti|first3=Robert S|last4=Gubler|first4=Duane J|title=West Nile virus|journal=The Lancet Infectious Diseases|volume=2|issue=9|year=2002|pages=519–529|issn=14733099|doi=10.1016/S1473-3099(02)00368-7}}</ref> It contains a single open reading frame ([[ORF]]), a 5' untranslated region ([[UTR]]), and another 3' region which is also not translated. The ORF contains a single polyprotein that produces 3 smaller types of structure proteins and 7 of non-structural proteins following processing and translation.
* Structural proteins are responsible for the formation of the viral particle and include:
:* Envelope proteins
:* Membrane proteins
:* C proteins
* Non-structural proteins are responsible for viral replication, evasion of the immune system, and assembly of virions. They include:
:*NS1
:*NS2A
:*NS2B
:*NS3
:*NS4A
:*NS4B
:*NS5

The WNV may be classified in 7 phylogenetic lineages. Of these, only 1 and 2 have been identified as causative agents of disease in humans and are considered clinically significant.<ref name=CDC>{{cite web | title = West Nile Virus | url = http://wwwnc.cdc.gov/eid/article/10/1/pdfs/02-0616.pdf }}</ref><ref name="pmid12890319">{{cite journal| author=Miller DL, Mauel MJ, Baldwin C, Burtle G, Ingram D, Hines ME et al.| title=West Nile virus in farmed alligators. | journal=Emerg Infect Dis | year= 2003 | volume= 9 | issue= 7 | pages= 794-9 | pmid=12890319 | doi=10.3201/eid0907.030085 | pmc=PMC3023431 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12890319 }} </ref><ref name="pmid16704810">{{cite journal| author=Bakonyi T, Ivanics E, Erdélyi K, Ursu K, Ferenczi E, Weissenböck H et al.| title=Lineage 1 and 2 strains of encephalitic West Nile virus, central Europe. | journal=Emerg Infect Dis | year= 2006 | volume= 12 | issue= 4 | pages= 618-23 | pmid=16704810 | doi=10.3201/eid1204.051379 | pmc=PMC3294705 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16704810 }} </ref><ref name="pmid14585341">{{cite journal| author=Charrel RN, Brault AC, Gallian P, Lemasson JJ, Murgue B, Murri S et al.| title=Evolutionary relationship between Old World West Nile virus strains. Evidence for viral gene flow between Africa, the Middle East, and Europe. | journal=Virology | year= 2003 | volume= 315 | issue= 2 | pages= 381-8 | pmid=14585341 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14585341 }} </ref><ref name="pmid12093177">{{cite journal| author=Lanciotti RS, Ebel GD, Deubel V, Kerst AJ, Murri S, Meyer R et al.| title=Complete genome sequences and phylogenetic analysis of West Nile virus strains isolated from the United States, Europe, and the Middle East. | journal=Virology | year= 2002 | volume= 298 | issue= 1 | pages= 96-105 | pmid=12093177 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12093177 }} </ref><ref name="pmid21781205">{{cite journal| author=Papa A, Xanthopoulou K, Gewehr S, Mourelatos S| title=Detection of West Nile virus lineage 2 in mosquitoes during a human outbreak in Greece. | journal=Clin Microbiol Infect | year= 2011 | volume= 17 | issue= 8 | pages= 1176-80 | pmid=21781205 | doi=10.1111/j.1469-0691.2010.03438.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21781205 }} </ref><ref name="pmid22406344">{{cite journal| author=Savini G, Capelli G, Monaco F, Polci A, Russo F, Di Gennaro A et al.| title=Evidence of West Nile virus lineage 2 circulation in Northern Italy. | journal=Vet Microbiol | year= 2012 | volume= 158 | issue= 3-4 | pages= 267-73 | pmid=22406344 | doi=10.1016/j.vetmic.2012.02.018 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22406344 }} </ref><ref name="pmid21586266">{{cite journal| author=Valiakos G, Touloudi A, Iacovakis C, Athanasiou L, Birtsas P, Spyrou V et al.| title=Molecular detection and phylogenetic analysis of West Nile virus lineage 2 in sedentary wild birds (Eurasian magpie), Greece, 2010. | journal=Euro Surveill | year= 2011 | volume= 16 | issue= 18 | pages= | pmid=21586266 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21586266 }} </ref>
* Lineage 1: Widespread, isolates from Europe, America, Middle East, India, Africa, and Australia
* Lingeage 2: Southern Africa, Madagascar, and Europe

==Natural reservoir==
Although WNV can infect humans and numerous animals, birds are its main [[natural reservoir]].<ref name="pmid23860989">{{cite journal| author=Petersen LR, Brault AC, Nasci RS| title=West Nile virus: review of the literature. | journal=JAMA | year= 2013 | volume= 310 | issue= 3 | pages= 308-15 | pmid=23860989 | doi=10.1001/jama.2013.8042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23860989 }} </ref><ref name="CampbellMarfin2002">{{cite journal|last1=Campbell|first1=Grant L|last2=Marfin|first2=Anthony A|last3=Lanciotti|first3=Robert S|last4=Gubler|first4=Duane J|title=West Nile virus|journal=The Lancet Infectious Diseases|volume=2|issue=9|year=2002|pages=519–529|issn=14733099|doi=10.1016/S1473-3099(02)00368-7}}</ref>

==Gallery==

<gallery>

Image: Flavivirus13.jpeg| West Nile virus is a flavivirus commonly found in Africa, West Asia, and the Middle East. ''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref>

Image: Flavivirus12.jpeg| This is a transmission electron micrograph (TEM) of the West Nile virus (WNV). ''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref>

Image: Flavivirus06.jpeg| Digitally-colorized transmission electron micrograph (TEM) of the West Nile virus (WNV). ''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref>
</gallery>

==References==
{{Reflist|2}}

West nile virus

2016-05-04T14:24:11Z

Sergekorjian:

__NOTOC__
{{West nile virus infection}}

{{About0|West nile virus infection}}

{{CMG}}

==Overview==
WNV is an enveloped positive-sense ssRNA virus of 11000 base pairs (bp) that is considered a member of the Japanese encephalitis serocomplex. It belongs to the genus Flavivirus and family Flaviviridae. Its RNA encodes structural and non-structural proteins. Although 7 lineages of WNV have been described, only lineage 1 and 2 are clinically significant. The viral natural reservoir includes many species, such as humans, horses, dogs, and cats; but the main natural reservoir is birds.

==Taxonomy==
Viruses; ssRNA viruses; ssRNA positive-strand viruses, no DNA stage; Flaviviridae; Flavivirus; Japanese encephalitis virus group<ref name=NCBI>{{cite web | title = West Nile Virus | url = http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=11082&lvl=3&lin=f&keep=1&srchmode=1&unlock }}</ref>

==Biology==

{| style="float: right;"

|
[[File:WNV.jpg|200px|thumb|none| Digitally-colorized transmission electron micrograph (TEM) of the West Nile virus (WNV). ''Image provided by the CDC [http://phil.cdc.gov/phil/details.asp Centers for Disease Control and Prevention] ''<ref>{{Cite web | title = http://phil.cdc.gov/phil/details.asp | url = http://phil.cdc.gov/phil/details.asp}}</ref>]]
|-
| [[File:WNV2.jpg|200px|thumb|none| Presence of West Nile virus virions, in an isolate that was grown in a cell culture. ''Image provided by the CDC [http://phil.cdc.gov/phil/details.asp Centers for Disease Control and Prevention] ''<ref>{{Cite web | title = http://phil.cdc.gov/phil/details.asp | url = http://phil.cdc.gov/phil/details.asp}}</ref>]]
|}
WNV is a member of Japanese encephalitis serocomplex and belongs to the [[genus]] [[Flavivirus]], family [[Flaviviridae]]. Other [[species]] of the this serocomplex include the [[St Louis encephalitis virus]] and the [[Japanese encephalitis virus]].<ref name="pmid23860989">{{cite journal| author=Petersen LR, Brault AC, Nasci RS| title=West Nile virus: review of the literature. | journal=JAMA | year= 2013 | volume= 310 | issue= 3 | pages= 308-15 | pmid=23860989 | doi=10.1001/jama.2013.8042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23860989 }} </ref>

The WNV has an icosahedral symmetry, with a smooth surface.<ref name="Mukhopadhyay2003">{{cite journal|last1=Mukhopadhyay|first1=S.|title=Structure of West Nile Virus|journal=Science|volume=302|issue=5643|year=2003|pages=248–248|issn=0036-8075|doi=10.1126/science.1089316}}</ref> It is an enveloped virus with a nucleocapsid core built of [[RNA]] and [[capsid]] proteins. Its [[genome]] is contained in a single-stranded [[RNA]] of about 11000 bp.<ref name="CampbellMarfin2002">{{cite journal|last1=Campbell|first1=Grant L|last2=Marfin|first2=Anthony A|last3=Lanciotti|first3=Robert S|last4=Gubler|first4=Duane J|title=West Nile virus|journal=The Lancet Infectious Diseases|volume=2|issue=9|year=2002|pages=519–529|issn=14733099|doi=10.1016/S1473-3099(02)00368-7}}</ref> It contains a single open reading frame ([[ORF]]), a 5' untranslated region ([[UTR]]), and another 3' region which is also not translated. The ORF contains a single polyprotein that produces 3 smaller types of structure proteins and 7 of non-structural proteins following processing and translation.
* Structural proteins are responsible for the formation of the viral particle and include:
:* Envelope proteins
:* Membrane proteins
:* C proteins
* Non-structural proteins are responsible for viral replication, evasion of the immune system, and assembly of virions. They include:
:*NS1
:*NS2A
:*NS2B
:*NS3
:*NS4A
:*NS4B
:*NS5

The WNV may be classified in 7 phylogenetic lineages. Of these, only 1 and 2 have been identified as causative agents of disease in humans and are considered clinically significant.<ref name=CDC>{{cite web | title = West Nile Virus | url = http://wwwnc.cdc.gov/eid/article/10/1/pdfs/02-0616.pdf }}</ref><ref name="pmid12890319">{{cite journal| author=Miller DL, Mauel MJ, Baldwin C, Burtle G, Ingram D, Hines ME et al.| title=West Nile virus in farmed alligators. | journal=Emerg Infect Dis | year= 2003 | volume= 9 | issue= 7 | pages= 794-9 | pmid=12890319 | doi=10.3201/eid0907.030085 | pmc=PMC3023431 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12890319 }} </ref><ref name="pmid16704810">{{cite journal| author=Bakonyi T, Ivanics E, Erdélyi K, Ursu K, Ferenczi E, Weissenböck H et al.| title=Lineage 1 and 2 strains of encephalitic West Nile virus, central Europe. | journal=Emerg Infect Dis | year= 2006 | volume= 12 | issue= 4 | pages= 618-23 | pmid=16704810 | doi=10.3201/eid1204.051379 | pmc=PMC3294705 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16704810 }} </ref><ref name="pmid14585341">{{cite journal| author=Charrel RN, Brault AC, Gallian P, Lemasson JJ, Murgue B, Murri S et al.| title=Evolutionary relationship between Old World West Nile virus strains. Evidence for viral gene flow between Africa, the Middle East, and Europe. | journal=Virology | year= 2003 | volume= 315 | issue= 2 | pages= 381-8 | pmid=14585341 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14585341 }} </ref><ref name="pmid12093177">{{cite journal| author=Lanciotti RS, Ebel GD, Deubel V, Kerst AJ, Murri S, Meyer R et al.| title=Complete genome sequences and phylogenetic analysis of West Nile virus strains isolated from the United States, Europe, and the Middle East. | journal=Virology | year= 2002 | volume= 298 | issue= 1 | pages= 96-105 | pmid=12093177 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12093177 }} </ref><ref name="pmid21781205">{{cite journal| author=Papa A, Xanthopoulou K, Gewehr S, Mourelatos S| title=Detection of West Nile virus lineage 2 in mosquitoes during a human outbreak in Greece. | journal=Clin Microbiol Infect | year= 2011 | volume= 17 | issue= 8 | pages= 1176-80 | pmid=21781205 | doi=10.1111/j.1469-0691.2010.03438.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21781205 }} </ref><ref name="pmid22406344">{{cite journal| author=Savini G, Capelli G, Monaco F, Polci A, Russo F, Di Gennaro A et al.| title=Evidence of West Nile virus lineage 2 circulation in Northern Italy. | journal=Vet Microbiol | year= 2012 | volume= 158 | issue= 3-4 | pages= 267-73 | pmid=22406344 | doi=10.1016/j.vetmic.2012.02.018 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22406344 }} </ref><ref name="pmid21586266">{{cite journal| author=Valiakos G, Touloudi A, Iacovakis C, Athanasiou L, Birtsas P, Spyrou V et al.| title=Molecular detection and phylogenetic analysis of West Nile virus lineage 2 in sedentary wild birds (Eurasian magpie), Greece, 2010. | journal=Euro Surveill | year= 2011 | volume= 16 | issue= 18 | pages= | pmid=21586266 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21586266 }} </ref>
* Lineage 1: Widespread, isolates from Europe, America, Middle East, India, Africa, and Australia
* Lingeage 2: Southern Africa, Madagascar, and Europe

==Natural reservoir==
Although WNV can infect humans and numerous animals, birds are its main [[natural reservoir]].<ref name="pmid23860989">{{cite journal| author=Petersen LR, Brault AC, Nasci RS| title=West Nile virus: review of the literature. | journal=JAMA | year= 2013 | volume= 310 | issue= 3 | pages= 308-15 | pmid=23860989 | doi=10.1001/jama.2013.8042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23860989 }} </ref><ref name="CampbellMarfin2002">{{cite journal|last1=Campbell|first1=Grant L|last2=Marfin|first2=Anthony A|last3=Lanciotti|first3=Robert S|last4=Gubler|first4=Duane J|title=West Nile virus|journal=The Lancet Infectious Diseases|volume=2|issue=9|year=2002|pages=519–529|issn=14733099|doi=10.1016/S1473-3099(02)00368-7}}</ref>

==Gallery==

<gallery>

Image: Flavivirus13.jpeg| West Nile virus is a flavivirus commonly found in Africa, West Asia, and the Middle East. ''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref>

Image: Flavivirus12.jpeg| This is a transmission electron micrograph (TEM) of the West Nile virus (WNV). ''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref>

Image: Flavivirus06.jpeg| Digitally-colorized transmission electron micrograph (TEM) of the West Nile virus (WNV). ''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref>
</gallery>

==References==
{{Reflist|2}}

West nile virus

2016-05-04T14:20:55Z

Sergekorjian:

__NOTOC__
{{West nile virus infection}}

{{About0|West nile virus infection}}

{{CMG}}

==Overview==
WNV is an enveloped positive-sense ssRNA virus of 11000 base pairs (bp) that is considered a member of the Japanese encephalitis serocomplex. It belongs to the genus Flavivirus and family Flaviviridae. Its RNA encodes structural and non-structural proteins. Although 7 lineages of WNV have been described, only lineage 1 and 2 are clinically significant. The viral natural reservoir includes many species, such as humans, horses, dogs, and cats; but the main natural reservoir is birds.

==Taxonomy==
Viruses; ssRNA viruses; ssRNA positive-strand viruses, no DNA stage; Flaviviridae; Flavivirus; Japanese encephalitis virus group<ref name=NCBI>{{cite web | title = West Nile Virus | url = http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=11082&lvl=3&lin=f&keep=1&srchmode=1&unlock }}</ref>

==Biology==

{| style="float: right;"

|
[[File:WNV.jpg|200px|thumb|none| Digitally-colorized transmission electron micrograph (TEM) of the West Nile virus (WNV). ''Image provided by the CDC [http://phil.cdc.gov/phil/details.asp Centers for Disease Control and Prevention] ''<ref>{{Cite web | title = http://phil.cdc.gov/phil/details.asp | url = http://phil.cdc.gov/phil/details.asp}}</ref>]]
|-
| [[File:WNV2.jpg|200px|thumb|none| Presence of West Nile virus virions, in an isolate that was grown in a cell culture. ''Image provided by the CDC [http://phil.cdc.gov/phil/details.asp Centers for Disease Control and Prevention] ''<ref>{{Cite web | title = http://phil.cdc.gov/phil/details.asp | url = http://phil.cdc.gov/phil/details.asp}}</ref>]]
|}
WNV is a member of Japanese encephalitis serocomplex and belongs to the [[genus]] [[Flavivirus]], family [[Flaviviridae]]. Other [[species]] of the this serocomplex include the [[St Louis encephalitis virus]] and the [[Japanese encephalitis virus]].<ref name="pmid23860989">{{cite journal| author=Petersen LR, Brault AC, Nasci RS| title=West Nile virus: review of the literature. | journal=JAMA | year= 2013 | volume= 310 | issue= 3 | pages= 308-15 | pmid=23860989 | doi=10.1001/jama.2013.8042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23860989 }} </ref>

The WNV has an icosahedral symmetry, with a smooth surface.<ref name="Mukhopadhyay2003">{{cite journal|last1=Mukhopadhyay|first1=S.|title=Structure of West Nile Virus|journal=Science|volume=302|issue=5643|year=2003|pages=248–248|issn=0036-8075|doi=10.1126/science.1089316}}</ref> It is an enveloped virus with a nucleocapsid core built of [[RNA]] and [[capsid]] proteins. Its [[genome]] is contained in a single-stranded [[RNA]] of about 11000 bp.<ref name="CampbellMarfin2002">{{cite journal|last1=Campbell|first1=Grant L|last2=Marfin|first2=Anthony A|last3=Lanciotti|first3=Robert S|last4=Gubler|first4=Duane J|title=West Nile virus|journal=The Lancet Infectious Diseases|volume=2|issue=9|year=2002|pages=519–529|issn=14733099|doi=10.1016/S1473-3099(02)00368-7}}</ref> It contains a single open reading frame ([[ORF]]), a 5' untranslated region ([[UTR]]), and another 3' region which is also not translated. The ORF contains a single polyprotein that produces 3 smaller types of structure proteins and 7 of non-structural proteins following processing and translation.
* Structural proteins are responsible for the formation of the viral particle and include:
:* Envelope proteins
:* Membrane proteins
:* C proteins
* Non-structural proteins are responsible for viral replication, evasion of the immune system, and assembly of virions. They include:
:*NS1
:*NS2A
:*NS2B
:*NS3
:*NS4A
:*NS4B
:*NS5

The WNV may be classified in 7 phylogenetic lineages. Of these, only 1 and 2 have been identified as causative agents of disease in humans and are considered clinically significant.<ref name=CDC>{{cite web | title = West Nile Virus | url = http://wwwnc.cdc.gov/eid/article/10/1/pdfs/02-0616.pdf }}</ref><ref name="pmid12890319">{{cite journal| author=Miller DL, Mauel MJ, Baldwin C, Burtle G, Ingram D, Hines ME et al.| title=West Nile virus in farmed alligators. | journal=Emerg Infect Dis | year= 2003 | volume= 9 | issue= 7 | pages= 794-9 | pmid=12890319 | doi=10.3201/eid0907.030085 | pmc=PMC3023431 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12890319 }} </ref><ref name="pmid16704810">{{cite journal| author=Bakonyi T, Ivanics E, Erdélyi K, Ursu K, Ferenczi E, Weissenböck H et al.| title=Lineage 1 and 2 strains of encephalitic West Nile virus, central Europe. | journal=Emerg Infect Dis | year= 2006 | volume= 12 | issue= 4 | pages= 618-23 | pmid=16704810 | doi=10.3201/eid1204.051379 | pmc=PMC3294705 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16704810 }} </ref><ref name="pmid14585341">{{cite journal| author=Charrel RN, Brault AC, Gallian P, Lemasson JJ, Murgue B, Murri S et al.| title=Evolutionary relationship between Old World West Nile virus strains. Evidence for viral gene flow between Africa, the Middle East, and Europe. | journal=Virology | year= 2003 | volume= 315 | issue= 2 | pages= 381-8 | pmid=14585341 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14585341 }} </ref><ref name="pmid12093177">{{cite journal| author=Lanciotti RS, Ebel GD, Deubel V, Kerst AJ, Murri S, Meyer R et al.| title=Complete genome sequences and phylogenetic analysis of West Nile virus strains isolated from the United States, Europe, and the Middle East. | journal=Virology | year= 2002 | volume= 298 | issue= 1 | pages= 96-105 | pmid=12093177 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12093177 }} </ref><ref name="pmid21781205">{{cite journal| author=Papa A, Xanthopoulou K, Gewehr S, Mourelatos S| title=Detection of West Nile virus lineage 2 in mosquitoes during a human outbreak in Greece. | journal=Clin Microbiol Infect | year= 2011 | volume= 17 | issue= 8 | pages= 1176-80 | pmid=21781205 | doi=10.1111/j.1469-0691.2010.03438.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21781205 }} </ref><ref name="pmid22406344">{{cite journal| author=Savini G, Capelli G, Monaco F, Polci A, Russo F, Di Gennaro A et al.| title=Evidence of West Nile virus lineage 2 circulation in Northern Italy. | journal=Vet Microbiol | year= 2012 | volume= 158 | issue= 3-4 | pages= 267-73 | pmid=22406344 | doi=10.1016/j.vetmic.2012.02.018 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22406344 }} </ref><ref name="pmid21586266">{{cite journal| author=Valiakos G, Touloudi A, Iacovakis C, Athanasiou L, Birtsas P, Spyrou V et al.| title=Molecular detection and phylogenetic analysis of West Nile virus lineage 2 in sedentary wild birds (Eurasian magpie), Greece, 2010. | journal=Euro Surveill | year= 2011 | volume= 16 | issue= 18 | pages= | pmid=21586266 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21586266 }} </ref>
* Lineage 1: Widespread, isolates from Europe, America, Middle East, India, Africa, and Australia
* Lingeage 2: Southern Africa, Madagascar, and Europe

==Natural reservoir==
Although WNV can infect humans and numerous animals, birds are its main [[natural reservoir]].<ref name="pmid23860989">{{cite journal| author=Petersen LR, Brault AC, Nasci RS| title=West Nile virus: review of the literature. | journal=JAMA | year= 2013 | volume= 310 | issue= 3 | pages= 308-15 | pmid=23860989 | doi=10.1001/jama.2013.8042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23860989 }} </ref><ref name="CampbellMarfin2002">{{cite journal|last1=Campbell|first1=Grant L|last2=Marfin|first2=Anthony A|last3=Lanciotti|first3=Robert S|last4=Gubler|first4=Duane J|title=West Nile virus|journal=The Lancet Infectious Diseases|volume=2|issue=9|year=2002|pages=519–529|issn=14733099|doi=10.1016/S1473-3099(02)00368-7}}</ref>

==Gallery==

<gallery>

Image: Flavivirus13.jpeg| West Nile virus is a flavivirus commonly found in Africa, West Asia, and the Middle East. ''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref>

Image: Flavivirus12.jpeg| This is a transmission electron micrograph (TEM) of the West Nile virus (WNV). ''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref>
</gallery>

Image: Flavivirus06.jpeg| Digitally-colorized transmission electron micrograph (TEM) of the West Nile virus (WNV). ''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref>

</gallery>

==References==
{{Reflist|2}}

West nile virus

2016-05-04T14:19:14Z

Sergekorjian: /* Biology */

{{West nile virus infection}}

{{About0|West nile virus infection}}

{{CMG}}

==Overview==
WNV is an enveloped positive-sense ssRNA virus of 11000 base pairs (bp) that is considered a member of the Japanese encephalitis serocomplex. It belongs to the genus Flavivirus and family Flaviviridae. Its RNA encodes structural and non-structural proteins. Although 7 lineages of WNV have been described, only lineage 1 and 2 are clinically significant. The viral natural reservoir includes many species, such as humans, horses, dogs, and cats; but the main natural reservoir is birds.

==Taxonomy==
Viruses; ssRNA viruses; ssRNA positive-strand viruses, no DNA stage; Flaviviridae; Flavivirus; Japanese encephalitis virus group<ref name=NCBI>{{cite web | title = West Nile Virus | url = http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=11082&lvl=3&lin=f&keep=1&srchmode=1&unlock }}</ref>

==Biology==

{| style="float: right;"

|
[[File:WNV.jpg|200px|thumb|none| Digitally-colorized transmission electron micrograph (TEM) of the West Nile virus (WNV). ''Image provided by the CDC [http://phil.cdc.gov/phil/details.asp Centers for Disease Control and Prevention] ''<ref>{{Cite web | title = http://phil.cdc.gov/phil/details.asp | url = http://phil.cdc.gov/phil/details.asp}}</ref>]]
|-
| [[File:WNV2.jpg|200px|thumb|none| Presence of West Nile virus virions, in an isolate that was grown in a cell culture. ''Image provided by the CDC [http://phil.cdc.gov/phil/details.asp Centers for Disease Control and Prevention] ''<ref>{{Cite web | title = http://phil.cdc.gov/phil/details.asp | url = http://phil.cdc.gov/phil/details.asp}}</ref>]]
|}
WNV is a member of Japanese encephalitis serocomplex and belongs to the [[genus]] [[Flavivirus]], family [[Flaviviridae]]. Other [[species]] of the this serocomplex include the [[St Louis encephalitis virus]] and the [[Japanese encephalitis virus]].<ref name="pmid23860989">{{cite journal| author=Petersen LR, Brault AC, Nasci RS| title=West Nile virus: review of the literature. | journal=JAMA | year= 2013 | volume= 310 | issue= 3 | pages= 308-15 | pmid=23860989 | doi=10.1001/jama.2013.8042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23860989 }} </ref>

The WNV has an icosahedral symmetry, with a smooth surface.<ref name="Mukhopadhyay2003">{{cite journal|last1=Mukhopadhyay|first1=S.|title=Structure of West Nile Virus|journal=Science|volume=302|issue=5643|year=2003|pages=248–248|issn=0036-8075|doi=10.1126/science.1089316}}</ref> It is an enveloped virus with a nucleocapsid core built of [[RNA]] and [[capsid]] proteins. Its [[genome]] is contained in a single-stranded [[RNA]] of about 11000 bp.<ref name="CampbellMarfin2002">{{cite journal|last1=Campbell|first1=Grant L|last2=Marfin|first2=Anthony A|last3=Lanciotti|first3=Robert S|last4=Gubler|first4=Duane J|title=West Nile virus|journal=The Lancet Infectious Diseases|volume=2|issue=9|year=2002|pages=519–529|issn=14733099|doi=10.1016/S1473-3099(02)00368-7}}</ref> It contains a single open reading frame ([[ORF]]), a 5' untranslated region ([[UTR]]), and another 3' region which is also not translated. The ORF contains a single polyprotein that produces 3 smaller types of structure proteins and 7 of non-structural proteins following processing and translation.
* Structural proteins are responsible for the formation of the viral particle and include:
:* Envelope proteins
:* Membrane proteins
:* C proteins
* Non-structural proteins are responsible for viral replication, evasion of the immune system, and assembly of virions. They include:
:*NS1
:*NS2A
:*NS2B
:*NS3
:*NS4A
:*NS4B
:*NS5

The WNV may be classified in 7 phylogenetic lineages. Of these, only 1 and 2 have been identified as causative agents of disease in humans and are considered clinically significant.<ref name=CDC>{{cite web | title = West Nile Virus | url = http://wwwnc.cdc.gov/eid/article/10/1/pdfs/02-0616.pdf }}</ref><ref name="pmid12890319">{{cite journal| author=Miller DL, Mauel MJ, Baldwin C, Burtle G, Ingram D, Hines ME et al.| title=West Nile virus in farmed alligators. | journal=Emerg Infect Dis | year= 2003 | volume= 9 | issue= 7 | pages= 794-9 | pmid=12890319 | doi=10.3201/eid0907.030085 | pmc=PMC3023431 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12890319 }} </ref><ref name="pmid16704810">{{cite journal| author=Bakonyi T, Ivanics E, Erdélyi K, Ursu K, Ferenczi E, Weissenböck H et al.| title=Lineage 1 and 2 strains of encephalitic West Nile virus, central Europe. | journal=Emerg Infect Dis | year= 2006 | volume= 12 | issue= 4 | pages= 618-23 | pmid=16704810 | doi=10.3201/eid1204.051379 | pmc=PMC3294705 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16704810 }} </ref><ref name="pmid14585341">{{cite journal| author=Charrel RN, Brault AC, Gallian P, Lemasson JJ, Murgue B, Murri S et al.| title=Evolutionary relationship between Old World West Nile virus strains. Evidence for viral gene flow between Africa, the Middle East, and Europe. | journal=Virology | year= 2003 | volume= 315 | issue= 2 | pages= 381-8 | pmid=14585341 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14585341 }} </ref><ref name="pmid12093177">{{cite journal| author=Lanciotti RS, Ebel GD, Deubel V, Kerst AJ, Murri S, Meyer R et al.| title=Complete genome sequences and phylogenetic analysis of West Nile virus strains isolated from the United States, Europe, and the Middle East. | journal=Virology | year= 2002 | volume= 298 | issue= 1 | pages= 96-105 | pmid=12093177 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12093177 }} </ref><ref name="pmid21781205">{{cite journal| author=Papa A, Xanthopoulou K, Gewehr S, Mourelatos S| title=Detection of West Nile virus lineage 2 in mosquitoes during a human outbreak in Greece. | journal=Clin Microbiol Infect | year= 2011 | volume= 17 | issue= 8 | pages= 1176-80 | pmid=21781205 | doi=10.1111/j.1469-0691.2010.03438.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21781205 }} </ref><ref name="pmid22406344">{{cite journal| author=Savini G, Capelli G, Monaco F, Polci A, Russo F, Di Gennaro A et al.| title=Evidence of West Nile virus lineage 2 circulation in Northern Italy. | journal=Vet Microbiol | year= 2012 | volume= 158 | issue= 3-4 | pages= 267-73 | pmid=22406344 | doi=10.1016/j.vetmic.2012.02.018 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22406344 }} </ref><ref name="pmid21586266">{{cite journal| author=Valiakos G, Touloudi A, Iacovakis C, Athanasiou L, Birtsas P, Spyrou V et al.| title=Molecular detection and phylogenetic analysis of West Nile virus lineage 2 in sedentary wild birds (Eurasian magpie), Greece, 2010. | journal=Euro Surveill | year= 2011 | volume= 16 | issue= 18 | pages= | pmid=21586266 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21586266 }} </ref>
* Lineage 1: Widespread, isolates from Europe, America, Middle East, India, Africa, and Australia
* Lingeage 2: Southern Africa, Madagascar, and Europe

==Natural reservoir==
Although WNV can infect humans and numerous animals, birds are its main [[natural reservoir]].<ref name="pmid23860989">{{cite journal| author=Petersen LR, Brault AC, Nasci RS| title=West Nile virus: review of the literature. | journal=JAMA | year= 2013 | volume= 310 | issue= 3 | pages= 308-15 | pmid=23860989 | doi=10.1001/jama.2013.8042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23860989 }} </ref><ref name="CampbellMarfin2002">{{cite journal|last1=Campbell|first1=Grant L|last2=Marfin|first2=Anthony A|last3=Lanciotti|first3=Robert S|last4=Gubler|first4=Duane J|title=West Nile virus|journal=The Lancet Infectious Diseases|volume=2|issue=9|year=2002|pages=519–529|issn=14733099|doi=10.1016/S1473-3099(02)00368-7}}</ref>

==Gallery==

<gallery>

Image: Flavivirus13.jpeg| West Nile virus is a flavivirus commonly found in Africa, West Asia, and the Middle East. ''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref>

Image: Flavivirus12.jpeg| This is a transmission electron micrograph (TEM) of the West Nile virus (WNV). ''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref>
</gallery>

Image: Flavivirus06.jpeg| Digitally-colorized transmission electron micrograph (TEM) of the West Nile virus (WNV). ''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref>

</gallery>

==References==
{{Reflist|2}}

Adrenal metastases

2016-04-25T15:07:40Z

Sergekorjian: /* Overview */

__NOTOC__
{{SI}}
{{CMG}} {{AE}} {{Ammu}}

==Overview==
The pathogenesis of adrenal metastases is characterized by metastases from renal cell carcinoma, melanoma, lung cancer, colorectal cancer, breast cancer and lymphoma. On gross pathology, a unilateral, small asymptomatic lesion is a characteristic finding of adrenal metastasis. Adrenal metastases must be differentiated from other diseases that cause tumors in adrenal gland such as nonfunctional adenoma, primary carcinoma in adrenal glands, adrenal cyst, and non-functional pheochromocytoma. Adrenal metastases are thought to be present in up to 27% of patients with known malignant epithelial tumors at autopsy. Symptoms of adrenal metastases may include [[dizziness]], [[faintness]], [[fatigue]], [[weakness]], and [[weight loss]]. CT is the imaging modality of choice for adrenal metastases. The mainstay of therapy for adrenal metastases is chemotherapy.

==Pathophysiology==
*Adrenal metastases occur secondary to hematogenous seeding of neoplastic cells from renal cell carcinoma, melanoma, lung cancer, colorectal cancer, breast cancer and lymphoma.
*On gross pathology, a unilateral, small asymptomatic lesion is a characteristic finding of an adrenal metastasis.

==Differentiating Adrenal metastases from other Diseases==
*Adrenal metastases must be differentiated from other diseases that cause tumors in adrenal gland such as:
:*Nonfunctional adenoma
:*Primary carcinoma in adrenal glands
:*[[Adrenal cyst]]
:*Non-functional [[pheochromocytoma]]

==Epidemiology and Demographics==
* Adrenal metastases are thought to be present in up to 27% of patients with known malignant epithelial tumors at autopsy.
== Natural History, Complications and Prognosis==
*If left untreated, 20-35% of patients with cancer may progress to develop adrenal metastases.<ref name="pmid11849252">{{cite journal| author=Lam KY, Lo CY| title=Metastatic tumours of the adrenal glands: a 30-year experience in a teaching hospital. | journal=Clin Endocrinol (Oxf) | year= 2002 | volume= 56 | issue= 1 | pages= 95-101 | pmid=11849252 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11849252 }} </ref>
*Complications of adrenal metastases include central necrosis with adrenal hemorrhage and paraneoplastic leukemoid reaction.

== Diagnosis ==
=== Symptoms ===
*Symptoms of adrenal metastases may include the following:
:*[[Dizziness]]
:*[[Faintness]]
:*[[Fatigue]]
:*[[Weakness]]
:*[[Weight loss]]
=== Physical Examination ===
*Patients with adrenal metastases usually appear cachectic.
*Physical examination may be remarkable for:
:*Abdominal mass

===Laboratory Findings===
*There are no specific laboratory findings associated with adrenal metastases.
===Imaging Findings===
*CT is the imaging modality of choice for adrenal metastases.
*On CT, adrenal metastases may demonstrate less than 50% washout.
*On MRI, adrenal metastases may demonstrate:
:* T1: usually exhibit low signal intensity
:* T2: usually exhibit high signal intensity
:* T1 C+ (Gd): usually has progressive enhancement after administration of contrast material.
== Treatment ==
=== Medical Therapy ===
*The mainstay of therapy for adrenal metastases is chemotherapy.
=== Surgery ===
*Adrenalectomy in conjunction with chemotherapy is the most common approach to the treatment of adrenal metastases if primary disease is well controlled and the only site of metastasis is the adrenal gland.
=== Prevention ===
*There are no primary preventive measures available for adrenal metastases.

==References==
{{Reflist|2}}
[[Category:oncology]]

Adrenal metastases

2016-04-25T15:06:46Z

Sergekorjian: /* Treatment */

__NOTOC__
{{SI}}
{{CMG}} {{AE}} {{Ammu}}

==Overview==
The pathogenesis of adrenal metastases is characterized by metastases from renal cell carcinoma, melanoma, lung cancer, colorectal cancer, breast cancer and lymphoma. On gross pathology, unilateral, small asymptomatic lesion are characteristic findings of adrenal metastases. Adrenal metastases must be differentiated from other diseases that cause tumors in adrenal gland such as nonfunctional adenoma, primary carcinoma in adrenal glands, adrenal cyst, and non-functional pheochromocytoma. Adrenal metastases are thought to be present in up to 27% of patients with known malignant epithelial tumors at autopsy. Symptoms of adrenal metastases may include [[dizziness]], [[faintness]], [[fatigue]], [[weakness]], and [[weight loss]]. CT is the imaging modality of choice for adrenal metastases. The mainstay of therapy for adrenal metastases is chemotherapy.

==Pathophysiology==
*Adrenal metastases occur secondary to hematogenous seeding of neoplastic cells from renal cell carcinoma, melanoma, lung cancer, colorectal cancer, breast cancer and lymphoma.
*On gross pathology, a unilateral, small asymptomatic lesion is a characteristic finding of an adrenal metastasis.

==Differentiating Adrenal metastases from other Diseases==
*Adrenal metastases must be differentiated from other diseases that cause tumors in adrenal gland such as:
:*Nonfunctional adenoma
:*Primary carcinoma in adrenal glands
:*[[Adrenal cyst]]
:*Non-functional [[pheochromocytoma]]

==Epidemiology and Demographics==
* Adrenal metastases are thought to be present in up to 27% of patients with known malignant epithelial tumors at autopsy.
== Natural History, Complications and Prognosis==
*If left untreated, 20-35% of patients with cancer may progress to develop adrenal metastases.<ref name="pmid11849252">{{cite journal| author=Lam KY, Lo CY| title=Metastatic tumours of the adrenal glands: a 30-year experience in a teaching hospital. | journal=Clin Endocrinol (Oxf) | year= 2002 | volume= 56 | issue= 1 | pages= 95-101 | pmid=11849252 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11849252 }} </ref>
*Complications of adrenal metastases include central necrosis with adrenal hemorrhage and paraneoplastic leukemoid reaction.

== Diagnosis ==
=== Symptoms ===
*Symptoms of adrenal metastases may include the following:
:*[[Dizziness]]
:*[[Faintness]]
:*[[Fatigue]]
:*[[Weakness]]
:*[[Weight loss]]
=== Physical Examination ===
*Patients with adrenal metastases usually appear cachectic.
*Physical examination may be remarkable for:
:*Abdominal mass

===Laboratory Findings===
*There are no specific laboratory findings associated with adrenal metastases.
===Imaging Findings===
*CT is the imaging modality of choice for adrenal metastases.
*On CT, adrenal metastases may demonstrate less than 50% washout.
*On MRI, adrenal metastases may demonstrate:
:* T1: usually exhibit low signal intensity
:* T2: usually exhibit high signal intensity
:* T1 C+ (Gd): usually has progressive enhancement after administration of contrast material.
== Treatment ==
=== Medical Therapy ===
*The mainstay of therapy for adrenal metastases is chemotherapy.
=== Surgery ===
*Adrenalectomy in conjunction with chemotherapy is the most common approach to the treatment of adrenal metastases if primary disease is well controlled and the only site of metastasis is the adrenal gland.
=== Prevention ===
*There are no primary preventive measures available for adrenal metastases.

==References==
{{Reflist|2}}
[[Category:oncology]]

Adrenal metastases

2016-04-25T15:05:51Z

Sergekorjian: /* Natural History, Complications and Prognosis */

__NOTOC__
{{SI}}
{{CMG}} {{AE}} {{Ammu}}

==Overview==
The pathogenesis of adrenal metastases is characterized by metastases from renal cell carcinoma, melanoma, lung cancer, colorectal cancer, breast cancer and lymphoma. On gross pathology, unilateral, small asymptomatic lesion are characteristic findings of adrenal metastases. Adrenal metastases must be differentiated from other diseases that cause tumors in adrenal gland such as nonfunctional adenoma, primary carcinoma in adrenal glands, adrenal cyst, and non-functional pheochromocytoma. Adrenal metastases are thought to be present in up to 27% of patients with known malignant epithelial tumors at autopsy. Symptoms of adrenal metastases may include [[dizziness]], [[faintness]], [[fatigue]], [[weakness]], and [[weight loss]]. CT is the imaging modality of choice for adrenal metastases. The mainstay of therapy for adrenal metastases is chemotherapy.

==Pathophysiology==
*Adrenal metastases occur secondary to hematogenous seeding of neoplastic cells from renal cell carcinoma, melanoma, lung cancer, colorectal cancer, breast cancer and lymphoma.
*On gross pathology, a unilateral, small asymptomatic lesion is a characteristic finding of an adrenal metastasis.

==Differentiating Adrenal metastases from other Diseases==
*Adrenal metastases must be differentiated from other diseases that cause tumors in adrenal gland such as:
:*Nonfunctional adenoma
:*Primary carcinoma in adrenal glands
:*[[Adrenal cyst]]
:*Non-functional [[pheochromocytoma]]

==Epidemiology and Demographics==
* Adrenal metastases are thought to be present in up to 27% of patients with known malignant epithelial tumors at autopsy.
== Natural History, Complications and Prognosis==
*If left untreated, 20-35% of patients with cancer may progress to develop adrenal metastases.<ref name="pmid11849252">{{cite journal| author=Lam KY, Lo CY| title=Metastatic tumours of the adrenal glands: a 30-year experience in a teaching hospital. | journal=Clin Endocrinol (Oxf) | year= 2002 | volume= 56 | issue= 1 | pages= 95-101 | pmid=11849252 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11849252 }} </ref>
*Complications of adrenal metastases include central necrosis with adrenal hemorrhage and paraneoplastic leukemoid reaction.

== Diagnosis ==
=== Symptoms ===
*Symptoms of adrenal metastases may include the following:
:*[[Dizziness]]
:*[[Faintness]]
:*[[Fatigue]]
:*[[Weakness]]
:*[[Weight loss]]
=== Physical Examination ===
*Patients with adrenal metastases usually appear cachectic.
*Physical examination may be remarkable for:
:*Abdominal mass

===Laboratory Findings===
*There are no specific laboratory findings associated with adrenal metastases.
===Imaging Findings===
*CT is the imaging modality of choice for adrenal metastases.
*On CT, adrenal metastases may demonstrate less than 50% washout.
*On MRI, adrenal metastases may demonstrate:
:* T1: usually exhibit low signal intensity
:* T2: usually exhibit high signal intensity
:* T1 C+ (Gd): usually has progressive enhancement after administration of contrast material.
== Treatment ==
=== Medical Therapy ===
*The mainstay of therapy for adrenal metastases is chemotherapy.
=== Surgery ===
*Adrenalectomy in conjunction with chemotherapy is the most common approach to the treatment of adrenal metastases if primary disease is well controlled and the only site of metastasis if adrenal gland.
=== Prevention ===
*There are no primary preventive measures available for adrenal metastases.
==References==
{{Reflist|2}}
[[Category:oncology]]

Adrenal metastases

2016-04-25T15:04:47Z

Sergekorjian: /* Pathophysiology */

__NOTOC__
{{SI}}
{{CMG}} {{AE}} {{Ammu}}

==Overview==
The pathogenesis of adrenal metastases is characterized by metastases from renal cell carcinoma, melanoma, lung cancer, colorectal cancer, breast cancer and lymphoma. On gross pathology, unilateral, small asymptomatic lesion are characteristic findings of adrenal metastases. Adrenal metastases must be differentiated from other diseases that cause tumors in adrenal gland such as nonfunctional adenoma, primary carcinoma in adrenal glands, adrenal cyst, and non-functional pheochromocytoma. Adrenal metastases are thought to be present in up to 27% of patients with known malignant epithelial tumors at autopsy. Symptoms of adrenal metastases may include [[dizziness]], [[faintness]], [[fatigue]], [[weakness]], and [[weight loss]]. CT is the imaging modality of choice for adrenal metastases. The mainstay of therapy for adrenal metastases is chemotherapy.

==Pathophysiology==
*Adrenal metastases occur secondary to hematogenous seeding of neoplastic cells from renal cell carcinoma, melanoma, lung cancer, colorectal cancer, breast cancer and lymphoma.
*On gross pathology, a unilateral, small asymptomatic lesion is a characteristic finding of an adrenal metastasis.

==Differentiating Adrenal metastases from other Diseases==
*Adrenal metastases must be differentiated from other diseases that cause tumors in adrenal gland such as:
:*Nonfunctional adenoma
:*Primary carcinoma in adrenal glands
:*[[Adrenal cyst]]
:*Non-functional [[pheochromocytoma]]

==Epidemiology and Demographics==
* Adrenal metastases are thought to be present in up to 27% of patients with known malignant epithelial tumors at autopsy.
== Natural History, Complications and Prognosis==
*If left untreated, 20-35% of patients with cancer may progress to develop adrenal metastases.<ref name="pmid11849252">{{cite journal| author=Lam KY, Lo CY| title=Metastatic tumours of the adrenal glands: a 30-year experience in a teaching hospital. | journal=Clin Endocrinol (Oxf) | year= 2002 | volume= 56 | issue= 1 | pages= 95-101 | pmid=11849252 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11849252 }} </ref>
*Common complication of adrenal metastases are central necrosis with adrenal hemorrhage and paraneoplastic leukemoid reaction.
== Diagnosis ==
=== Symptoms ===
*Symptoms of adrenal metastases may include the following:
:*[[Dizziness]]
:*[[Faintness]]
:*[[Fatigue]]
:*[[Weakness]]
:*[[Weight loss]]
=== Physical Examination ===
*Patients with adrenal metastases usually appear cachectic.
*Physical examination may be remarkable for:
:*Abdominal mass

===Laboratory Findings===
*There are no specific laboratory findings associated with adrenal metastases.
===Imaging Findings===
*CT is the imaging modality of choice for adrenal metastases.
*On CT, adrenal metastases may demonstrate less than 50% washout.
*On MRI, adrenal metastases may demonstrate:
:* T1: usually exhibit low signal intensity
:* T2: usually exhibit high signal intensity
:* T1 C+ (Gd): usually has progressive enhancement after administration of contrast material.
== Treatment ==
=== Medical Therapy ===
*The mainstay of therapy for adrenal metastases is chemotherapy.
=== Surgery ===
*Adrenalectomy in conjunction with chemotherapy is the most common approach to the treatment of adrenal metastases if primary disease is well controlled and the only site of metastasis if adrenal gland.
=== Prevention ===
*There are no primary preventive measures available for adrenal metastases.
==References==
{{Reflist|2}}
[[Category:oncology]]

Adrenal metastases

2016-04-25T14:58:39Z

Sergekorjian: /* Differentiating Adrenal metastases from other Diseases */

__NOTOC__
{{SI}}
{{CMG}} {{AE}} {{Ammu}}

==Overview==
The pathogenesis of adrenal metastases is characterized by metastases from renal cell carcinoma, melanoma, lung cancer, colorectal cancer, breast cancer and lymphoma. On gross pathology, unilateral, small asymptomatic lesion are characteristic findings of adrenal metastases. Adrenal metastases must be differentiated from other diseases that cause tumors in adrenal gland such as nonfunctional adenoma, primary carcinoma in adrenal glands, adrenal cyst, and non-functional pheochromocytoma. Adrenal metastases are thought to be present in up to 27% of patients with known malignant epithelial tumors at autopsy. Symptoms of adrenal metastases may include [[dizziness]], [[faintness]], [[fatigue]], [[weakness]], and [[weight loss]]. CT is the imaging modality of choice for adrenal metastases. The mainstay of therapy for adrenal metastases is chemotherapy.

==Pathophysiology==
*The pathogenesis of adrenal metastases is characterized by metastases from renal cell carcinoma, melanoma, lung cancer, colorectal cancer, breast cancer and lymphoma.
*On gross pathology, unilateral, small asymptomatic lesion are characteristic findings of adrenal metastases.
==Differentiating Adrenal metastases from other Diseases==
*Adrenal metastases must be differentiated from other diseases that cause tumors in adrenal gland such as:
:*Nonfunctional adenoma
:*Primary carcinoma in adrenal glands
:*[[Adrenal cyst]]
:*Non-functional [[pheochromocytoma]]

==Epidemiology and Demographics==
* Adrenal metastases are thought to be present in up to 27% of patients with known malignant epithelial tumors at autopsy.
== Natural History, Complications and Prognosis==
*If left untreated, 20-35% of patients with cancer may progress to develop adrenal metastases.<ref name="pmid11849252">{{cite journal| author=Lam KY, Lo CY| title=Metastatic tumours of the adrenal glands: a 30-year experience in a teaching hospital. | journal=Clin Endocrinol (Oxf) | year= 2002 | volume= 56 | issue= 1 | pages= 95-101 | pmid=11849252 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11849252 }} </ref>
*Common complication of adrenal metastases are central necrosis with adrenal hemorrhage and paraneoplastic leukemoid reaction.
== Diagnosis ==
=== Symptoms ===
*Symptoms of adrenal metastases may include the following:
:*[[Dizziness]]
:*[[Faintness]]
:*[[Fatigue]]
:*[[Weakness]]
:*[[Weight loss]]
=== Physical Examination ===
*Patients with adrenal metastases usually appear cachectic.
*Physical examination may be remarkable for:
:*Abdominal mass

===Laboratory Findings===
*There are no specific laboratory findings associated with adrenal metastases.
===Imaging Findings===
*CT is the imaging modality of choice for adrenal metastases.
*On CT, adrenal metastases may demonstrate less than 50% washout.
*On MRI, adrenal metastases may demonstrate:
:* T1: usually exhibit low signal intensity
:* T2: usually exhibit high signal intensity
:* T1 C+ (Gd): usually has progressive enhancement after administration of contrast material.
== Treatment ==
=== Medical Therapy ===
*The mainstay of therapy for adrenal metastases is chemotherapy.
=== Surgery ===
*Adrenalectomy in conjunction with chemotherapy is the most common approach to the treatment of adrenal metastases if primary disease is well controlled and the only site of metastasis if adrenal gland.
=== Prevention ===
*There are no primary preventive measures available for adrenal metastases.
==References==
{{Reflist|2}}
[[Category:oncology]]

Adrenal metastases

2016-04-25T14:58:18Z

Sergekorjian: /* Overview */

__NOTOC__
{{SI}}
{{CMG}} {{AE}} {{Ammu}}

==Overview==
The pathogenesis of adrenal metastases is characterized by metastases from renal cell carcinoma, melanoma, lung cancer, colorectal cancer, breast cancer and lymphoma. On gross pathology, unilateral, small asymptomatic lesion are characteristic findings of adrenal metastases. Adrenal metastases must be differentiated from other diseases that cause tumors in adrenal gland such as nonfunctional adenoma, primary carcinoma in adrenal glands, adrenal cyst, and non-functional pheochromocytoma. Adrenal metastases are thought to be present in up to 27% of patients with known malignant epithelial tumors at autopsy. Symptoms of adrenal metastases may include [[dizziness]], [[faintness]], [[fatigue]], [[weakness]], and [[weight loss]]. CT is the imaging modality of choice for adrenal metastases. The mainstay of therapy for adrenal metastases is chemotherapy.

==Pathophysiology==
*The pathogenesis of adrenal metastases is characterized by metastases from renal cell carcinoma, melanoma, lung cancer, colorectal cancer, breast cancer and lymphoma.
*On gross pathology, unilateral, small asymptomatic lesion are characteristic findings of adrenal metastases.
==Differentiating Adrenal metastases from other Diseases==
*Adrenal metastases must be differentiated from other diseases that cause tumors in adrenal gland such as:
:*Nonfunctional adenoma
:*Adrenal metastasis
:*Primary carcinoma in adrenal glands
:*[[Adrenal cyst]]
:*Nonfunctional [[pheochromocytoma]]

==Epidemiology and Demographics==
* Adrenal metastases are thought to be present in up to 27% of patients with known malignant epithelial tumors at autopsy.
== Natural History, Complications and Prognosis==
*If left untreated, 20-35% of patients with cancer may progress to develop adrenal metastases.<ref name="pmid11849252">{{cite journal| author=Lam KY, Lo CY| title=Metastatic tumours of the adrenal glands: a 30-year experience in a teaching hospital. | journal=Clin Endocrinol (Oxf) | year= 2002 | volume= 56 | issue= 1 | pages= 95-101 | pmid=11849252 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11849252 }} </ref>
*Common complication of adrenal metastases are central necrosis with adrenal hemorrhage and paraneoplastic leukemoid reaction.
== Diagnosis ==
=== Symptoms ===
*Symptoms of adrenal metastases may include the following:
:*[[Dizziness]]
:*[[Faintness]]
:*[[Fatigue]]
:*[[Weakness]]
:*[[Weight loss]]
=== Physical Examination ===
*Patients with adrenal metastases usually appear cachectic.
*Physical examination may be remarkable for:
:*Abdominal mass

===Laboratory Findings===
*There are no specific laboratory findings associated with adrenal metastases.
===Imaging Findings===
*CT is the imaging modality of choice for adrenal metastases.
*On CT, adrenal metastases may demonstrate less than 50% washout.
*On MRI, adrenal metastases may demonstrate:
:* T1: usually exhibit low signal intensity
:* T2: usually exhibit high signal intensity
:* T1 C+ (Gd): usually has progressive enhancement after administration of contrast material.
== Treatment ==
=== Medical Therapy ===
*The mainstay of therapy for adrenal metastases is chemotherapy.
=== Surgery ===
*Adrenalectomy in conjunction with chemotherapy is the most common approach to the treatment of adrenal metastases if primary disease is well controlled and the only site of metastasis if adrenal gland.
=== Prevention ===
*There are no primary preventive measures available for adrenal metastases.
==References==
{{Reflist|2}}
[[Category:oncology]]

Peritoneal carcinomatosis

2016-04-25T14:38:42Z

Sergekorjian: /* Classification */

__NOTOC__
{{SI}}
{{CMG}} {{AE}} {{MV}}

{{SK}} Peritoneal metastases; Peritoneal seeding

==Overview==

'''Peritoneal carcinomatosis''' (also known as ''peritoneal metastases'') is defined as a malignant tumoral seeding of the peritoneum. Peritoneal metastases are the most common peritoneal malignancy, these commonly arise from [[ovarian cancer]], [[colon cancer]], [[gastric cancer]], and [[pancreatic cancer]]. Calcified peritoneal carcinomatosis may occur in serous ovarian adenocarcinoma, colon cancer, and gastric cancer. Peritoneal carcinogenesis arises from the celomic epithelium lining of the [[abdominal cavity]] (peritoneum) in response to an oncogenic stimulus.<ref name="pmid10228488">{{cite journal |vauthors=Deraco M, Santoro N, Carraro O, Inglese MG, Rebuffoni G, Guadagni S, Somers DC, Vaglini M |title=Peritoneal carcinomatosis: feature of dissemination. A review |journal=Tumori |volume=85 |issue=1 |pages=1–5 |year=1999 |pmid=10228488 |doi= |url=}}</ref> Common causes of peritoneal carcinomatosis, include: [[Peritoneal mesothelioma|peritoneal mesothelioma,]] [[Colon cancer|colon cancer,]] [[gastric cancer]], and [[pancreatic cancer]]. Early clinical features include [[abdominal pain]], [[abdominal distension]], and [[nausea]]. If left untreated, the majority of patients with peritoneal carcinomatosis may progress to develop [[portal hypertension]], [[pulmonary edema]], and death. Common complications of peritoneal carcinomatosis include [[intestinal obstruction]] and [[Pulmonary embolism|pulmonary thromboembolism]]. The diagnosis of peritoneal carcinomatosis, include: imaging findings compatible with peritoneal carcinomatosis, elevated protein concentration (more than 4.0 g/dL) in ascitic fluid, abnormal [[serum-ascites albumin gradient]] (less than 1.1 g/dL) in ascitic fluid, and high cell count (lymphocyte predominance). The mainstay medical therapy for peritoneal carcinomatosis is hyperthermic intraperitoneal chemotherapy (HIPEC), followed by cytoreductive surgery, [[laparotomy]] in conjunction with cytology testing is the most common approach for the treatment of peritoneal carcinomatosis. Prognosis is generally poor, and the 5-year survival rate of patients with peritoneal carcinomatosis is approximately 20%.<ref name="pmid24201391">{{cite journal |vauthors=Thomassen I, van Gestel YR, Lemmens VE, de Hingh IH |title=Incidence, prognosis, and treatment options for patients with synchronous peritoneal carcinomatosis and liver metastases from colorectal origin |journal=Dis. Colon Rectum |volume=56 |issue=12 |pages=1373–80 |year=2013 |pmid=24201391 |doi=10.1097/DCR.0b013e3182a62d9d |url=}}</ref>

==Historical Perspective==
*Peritoneal carcinomatosis was first described by Swerdlow in 1959.<ref name="PPP">Swerdlow M: Mesothelioma of the pelvic peritoneum resembling papillary cystadenocarcinoma of the ovary: Case report. Am J Obstet Gynecol 77:200, 1959.</ref>

==Classification==
*According to the Gilly classification, peritoneal carcinomatosis may be classified according to nodule size and intraperitoneal involvement (localized or diffuse) into 4 categories:<ref name="pmid20424420">{{cite journal |vauthors=Kianmanesh R, Ruszniewski P, Rindi G, Kwekkeboom D, Pape UF, Kulke M, Sevilla Garcia I, Scoazec JY, Nilsson O, Fazio N, Lesurtel M, Chen YJ, Eriksson B, Cioppi F, O'Toole D |title=ENETS consensus guidelines for the management of peritoneal carcinomatosis from neuroendocrine tumors |journal=Neuroendocrinology |volume=91 |issue=4 |pages=333–40 |year=2010 |pmid=20424420 |doi=10.1159/000286700 |url=}}</ref>
:*0 - No macroscopic disease
:*1 - Malignant granulations less than 5 mm in diameter localized in one part of the abdomen
:*2 - Malignant granulations less than 5 mm in diameter diffuse to the whole abdomen
:*3 - Localized or diffuse malignant granulations 5–20 mm in diameter
:*4 - Localized or diffuse large malignant masses (more than 2 cm in diameter)

==Pathophysiology==
*The pathogenesis of peritoneal carcinomatosis is characterized by the malignant seeding of a tumor in the peritoneal cavity.<ref name="pmid10228488">{{cite journal |vauthors=Deraco M, Santoro N, Carraro O, Inglese MG, Rebuffoni G, Guadagni S, Somers DC, Vaglini M |title=Peritoneal carcinomatosis: feature of dissemination. A review |journal=Tumori |volume=85 |issue=1 |pages=1–5 |year=1999 |pmid=10228488 |doi= |url=}}</ref>
*Peritoneal carcinogenesis arises from the celomic epithelium lining of the [[abdominal cavity]] (peritoneum) in response to an oncogenic stimulus.<ref name="pmid10228488">{{cite journal |vauthors=Deraco M, Santoro N, Carraro O, Inglese MG, Rebuffoni G, Guadagni S, Somers DC, Vaglini M |title=Peritoneal carcinomatosis: feature of dissemination. A review |journal=Tumori |volume=85 |issue=1 |pages=1–5 |year=1999 |pmid=10228488 |doi= |url=}}</ref>
*The mutation on [[BRCA|BRCA1/BRCA2]] has been associated with the development of peritoneal carcinomatosis.
*On gross pathology, characteristic findings of peritoneal carcinomatosis, include:<ref name="wiki">Peritoneum. Libre patholgy. https://librepathology.org/wiki/Peritoneum Accessed on April 7, 2016</ref>
:*Multilocular thin-walled cysts containing serous fluid
:*Occasionally unilocular
:*May be up to 15 cm
:*Adherent to the surface
*On microscopic histopathological analysis, characteristic findings of peritoneal carcinomatosis, include:<ref name="wiki">Peritoneum. Libre patholgy. https://librepathology.org/wiki/Peritoneum Accessed on April 7, 2016</ref>
:*Thin-walled, irregular-shaped cysts
:*Mesothelial lining
:*[[Squamous metaplasia]]
:*Eosinophilic fluid

==Causes==
* Common causes of peritoneal carcinomatosis, include:<ref name="wiki">Peritoneal carcinomatosis. Wikipedia. https://en.wikipedia.org/wiki/Primary_peritoneal_carcinoma Accessed on April 7, 2016</ref>
:*[[Peritoneal mesothelioma]]
:*[[Colon cancer]]
:*[[Gastric cancer]]
:*[[Pancreatic cancer]]
* Peritoneal carcinomatosis may also be caused by a mutation in the BCRA1 or BCRA2 genes.

==Differentiating Peritoneal Carcinomatosis from Other Diseases==
*Peritoneal carcinomatosis must be differentiated from other diseases that cause abdominal pain, ascites, and weight loss, such as:<ref name="wiki">Peritoneal metastases. Dr Henry Knipe. Radiopedia http://radiopaedia.org/articles/peritoneal-metastases Accessed on April 7, 2016</ref>
:*[[Peritoneal mesothelioma]]
:*[[Tuberculosis|Peritoneal tuberculosis]]
:*[[Pseudomyxoma peritonei]]

==Epidemiology and Demographics==
* The prevalence of peritoneal carcinomatosis is approximately 0.03 per 100,000 individuals worldwide.<ref name="pmid22287157">{{cite journal |vauthors=Segelman J, Granath F, Holm T, Machado M, Mahteme H, Martling A |title=Incidence, prevalence and risk factors for peritoneal carcinomatosis from colorectal cancer |journal=Br J Surg |volume=99 |issue=5 |pages=699–705 |year=2012 |pmid=22287157 |doi=10.1002/bjs.8679 |url=}}</ref>
===Age===
*Peritoneal carcinomatosis is more commonly observed among patients aged 50 - 70 years.<ref name="pmid8519536">{{cite journal |vauthors=Villanueva A, Pérez C, Sabaté JM, Llauger J, Giménez A, Sanchis E, García T, Moreno A |title=[Peritoneal carcinomatosis. Review of CT findings in 107 cases] |language=Spanish; Castilian |journal=Rev Esp Enferm Dig |volume=87 |issue=10 |pages=707–14 |year=1995 |pmid=8519536 |doi= |url=}}</ref>
*Peritoneal carcinomatosis is more commonly observed among adults.<ref name="pmid21160812">{{cite journal |vauthors=Kusamura S, Baratti D, Zaffaroni N, Villa R, Laterza B, Balestra MR, Deraco M |title=Pathophysiology and biology of peritoneal carcinomatosis |journal=World J Gastrointest Oncol |volume=2 |issue=1 |pages=12–8 |year=2010 |pmid=21160812 |pmc=2999153 |doi=10.4251/wjgo.v2.i1.12 |url=}}</ref>
===Gender===
*Females are more commonly affected with peritoneal carcinomatosis than males.<ref name="pmid21160812">{{cite journal |vauthors=Kusamura S, Baratti D, Zaffaroni N, Villa R, Laterza B, Balestra MR, Deraco M |title=Pathophysiology and biology of peritoneal carcinomatosis |journal=World J Gastrointest Oncol |volume=2 |issue=1 |pages=12–8 |year=2010 |pmid=21160812 |pmc=2999153 |doi=10.4251/wjgo.v2.i1.12 |url=}}</ref>
===Race===
*There is no racial predilection for peritoneal carcinomatosis.<ref name="pmid21160812">{{cite journal |vauthors=Kusamura S, Baratti D, Zaffaroni N, Villa R, Laterza B, Balestra MR, Deraco M |title=Pathophysiology and biology of peritoneal carcinomatosis |journal=World J Gastrointest Oncol |volume=2 |issue=1 |pages=12–8 |year=2010 |pmid=21160812 |pmc=2999153 |doi=10.4251/wjgo.v2.i1.12 |url=}}</ref>

==Risk Factors==
*The most important risk factor in the development of peritoneal carcinomatosis is the presence of [[ovarian cancer]], [[colon cancer]], [[gastric cancer]], and [[pancreatic cancer]].

== Natural History, Complications and Prognosis==
*The majority of patients with peritoneal carcinomatosis may be initially [[asymptomatic]].
*Early clinical features include [[abdominal pain]], [[abdominal distension]], and [[nausea]].
*If left untreated, the majority of patients with peritoneal carcinomatosis may progress to develop [[portal hypertension]], [[pulmonary edema]], and death.
*Common complications of peritoneal carcinomatosis include [[intestinal obstruction]] and [[Pulmonary embolism|pulmonary thromboembolism]].
*Prognosis is generally poor, and the 5 year survival rate of patients with peritoneal carcinomatosis is approximately 20%.

== Diagnosis ==
===Diagnostic Criteria===
*The diagnosis of peritoneal carcinomatosis is made when at least the following diagnostic criteria are met:<ref name="pmid8519536">{{cite journal |vauthors=Villanueva A, Pérez C, Sabaté JM, Llauger J, Giménez A, Sanchis E, García T, Moreno A |title=[Peritoneal carcinomatosis. Review of CT findings in 107 cases] |language=Spanish; Castilian |journal=Rev Esp Enferm Dig |volume=87 |issue=10 |pages=707–14 |year=1995 |pmid=8519536 |doi= |url=}}</ref>
:*Imaging findings compatible with peritoneal carcinomatosis (see below)
:*Elevated protein concentration (more than 4.0 g/dL)
:*Abnormal [[serum-ascites albumin gradient]] (less than 1.1 g/dL)
:*High cell count (lymphocyte predominance)

=== Symptoms ===
*Peritoneal carcinomatosis is usually asymptomatic.
*Symptoms of peritoneal carcinomatosis may include the following:<ref name="wiki">Peritoneal carcinomatosis. Wikipedia. https://en.wikipedia.org/wiki/Primary_peritoneal_carcinoma Accessed on April 7, 2016</ref>
:*[[Abdominal distension]]
:*[[Nausea]]
:*[[Bloating]]
:*[[Abdominal pain|Intermittent abdominal pain]]
:*[[Vomiting]]
:*Alternating [[diarrhea]] and [[constipation]]

=== Physical Examination ===
*Patients with peritoneal carcinomatosis usually appear pale and lethargic.
*Physical examination may be remarkable for:<ref name="wiki">Peritoneal carcinomatosis. Wikipedia. https://en.wikipedia.org/wiki/Primary_peritoneal_carcinoma Accessed on April 7, 2016</ref>
'''Inspection'''
:* Enlarged abdomen
:* Abdominal distension
'''Palpation'''
:*Bulging of the flanks or shifting dullness
:*Fluid thrill or fluid wave
*Other physical examination findings may include:
:*[[Leg swelling]]
:*[[Bruising]]
:*[[Gynecomastia]]

=== Laboratory Findings ===
*Laboratory findings consistent with the diagnosis of peritoneal carcinomatosis, include:<ref name="pmid21160812">{{cite journal |vauthors=Kusamura S, Baratti D, Zaffaroni N, Villa R, Laterza B, Balestra MR, Deraco M |title=Pathophysiology and biology of peritoneal carcinomatosis |journal=World J Gastrointest Oncol |volume=2 |issue=1 |pages=12–8 |year=2010 |pmid=21160812 |pmc=2999153 |doi=10.4251/wjgo.v2.i1.12 |url=}}</ref>
:* Elevated [[carcinoembryonic antigen]] (unspecific)
:* Elevated [[CA125|cancer antigen 125]] (unspecific)
:* Elevated [[CA 19-9|cancer antigen 19-9]] (unspecific)

===Imaging Findings===
*[[CT scan|Enhanced CT scan]] is the imaging modality of choice for peritoneal carcinomatosis.<ref name="pmid8519536">{{cite journal |vauthors=Villanueva A, Pérez C, Sabaté JM, Llauger J, Giménez A, Sanchis E, García T, Moreno A |title=[Peritoneal carcinomatosis. Review of CT findings in 107 cases] |language=Spanish; Castilian |journal=Rev Esp Enferm Dig |volume=87 |issue=10 |pages=707–14 |year=1995 |pmid=8519536 |doi= |url=}}</ref>
*On CT, peritoneal carcinomatosis is characterized by the following findings:<ref name="wiki">Peritoneal metastases. Dr Henry Knipe. Radiopedia http://radiopaedia.org/articles/peritoneal-metastases Accessed on April 7, 2016</ref>
:* Smooth or nodular peritoneal thickening and enhancement.
:* Implants on the liver and the splenic surfaces are frequently seen and result in scalloping of the surface by the masses.
:* Sites of tumor implantation are the intersegmental fissure, superior recess of the lesser sac, subphrenic space, and Morison pouch.
:* Usually there is large ascites, which is often loculated.
*The images below demonstrate a case of peritoneal carcinomatosis.
<gallery>
Image:

Carcinomatosis-001.jpg

Image:

Carcinomatosis-002.jpg

Image:

Carcinomatosis-003.jpg

</gallery>

=== Other Diagnostic Studies ===
*Peritoneal carcinomatosis may also be diagnosed using abdominal paracentesis.
*Findings on [[paracentesis]] may include:
:*Opalescent appearance
:*Elevated protein concentration (more than 4.0 g/dL)
:*Abnormal [[serum-ascites albumin gradient]] ( less than 1.1 g/dL )
*Other diagnostic studies, include: [[positron emission tomography]] (PET)/PET-CT, [[Laparoscopy|diagnostic laparoscopy]], [[ultrasonography]], [[magnetic resonance imaging]] (MRI)

== Treatment ==
=== Medical Therapy ===
*The mainstay medical therapy for peritoneal carcinomatosis is hyperthermic intraperitoneal chemotherapy (HIPEC).<ref name="pmid19133112">{{cite journal |vauthors=Glockzin G, Schlitt HJ, Piso P |title=Peritoneal carcinomatosis: patients selection, perioperative complications and quality of life related to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy |journal=World J Surg Oncol |volume=7 |issue= |pages=5 |year=2009 |pmid=19133112 |pmc=2639355 |doi=10.1186/1477-7819-7-5 |url=}}</ref>
*Common chemotherapy agents, include:<ref name="pmid19133112">{{cite journal |vauthors=Glockzin G, Schlitt HJ, Piso P |title=Peritoneal carcinomatosis: patients selection, perioperative complications and quality of life related to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy |journal=World J Surg Oncol |volume=7 |issue= |pages=5 |year=2009 |pmid=19133112 |pmc=2639355 |doi=10.1186/1477-7819-7-5 |url=}}</ref>
:*[[Mitomycin]]
:*[[Cisplatin]]
:*[[Oxaliplatin]]
:*[[Doxorubicin]]
:*[[Mitoxantrone]]

=== Surgery ===
*Cytoreductive surgery is the mainstay of therapy for peritoneal carcinomatosis.<ref name="pmid19133112">{{cite journal |vauthors=Glockzin G, Schlitt HJ, Piso P |title=Peritoneal carcinomatosis: patients selection, perioperative complications and quality of life related to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy |journal=World J Surg Oncol |volume=7 |issue= |pages=5 |year=2009 |pmid=19133112 |pmc=2639355 |doi=10.1186/1477-7819-7-5 |url=}}</ref>
*[[Laparotomy]] in conjunction with cytology testing is the most common approach to the treatment of peritoneal carcinomatosis.
*Cytoreductive surgery is composed of three steps: exploration of the abdominal cavity, debulking and chemoperfusion.

=== Prevention ===
*There are no primary preventive measures available for peritoneal carcinomatosis.
*Once diagnosed and successfully treated, patients with peritoneal carcinomatosis are followed-up every 1, 3 or 6 months.
*Follow-up testing includes ultrasound, paracentesis, and abdominal examination.<ref name="pmid8519536">{{cite journal |vauthors=Villanueva A, Pérez C, Sabaté JM, Llauger J, Giménez A, Sanchis E, García T, Moreno A |title=[Peritoneal carcinomatosis. Review of CT findings in 107 cases] |language=Spanish; Castilian |journal=Rev Esp Enferm Dig |volume=87 |issue=10 |pages=707–14 |year=1995 |pmid=8519536 |doi= |url=}}</ref>

==References==
{{Reflist|2}}

[[Category: Oncology]]

Mixed mullerian tumor

2016-04-22T14:59:45Z

Sergekorjian: /* Overview */

__NOTOC__
{{SI}}
{{CMG}} {{AE}} {{MV}}

{{SK}} Mixed Müllerian tumor; MMMT; Malignant mixed Müllerian tumor; Carcinosarcoma of the uterus; Sarcomatoid carcinoma of the uterus; Malignant mesodermal mixed tumor; Metaplastic carcinoma

==Overview==

'''Malignant mixed mullerian tumor''' (MMMT) is a rare [[uterine sarcoma]] or carcinosarcoma. Mixed Mullerian tumors are normally composed of both carcinomatous (epithelial) and sarcomatous (mesodermal) components. Mixed Mullerian tumor may be classified according to pathology findings into 2 types: epitheloid subtype and sarcomatoid subtype. Mixed Mullerian tumor may also be classified according to anatomical location into 7 types: [[Uterine corpus cancer|uterine corpus]], [[cervix]], [[ovaries]], [[fallopian tubes]], [[Vaginal Cancer|vagina]], [[peritoneum]], and extragenital sites. Common risk factors in the development of mixed Mullerian tumor are [[Radiation|exposure to radiation]], [[Estrogen|excessive estrogen exposure]], [[obesity]], and nulliparity.<ref name="pmid20642852">{{cite journal |vauthors=Kanthan R, Senger JL, Diudea D |title=Malignant mixed Mullerian tumors of the uterus: histopathological evaluation of cell cycle and apoptotic regulatory proteins |journal=World J Surg Oncol |volume=8 |issue= |pages=60 |year=2010 |pmid=20642852 |pmc=2913917 |doi=10.1186/1477-7819-8-60 |url=}}</ref> Mixed Mullerian tumor is more commonly observed among postmenopausal women between 50 and 60 years old. Early clinical features include [[Vaginal bleeding|postmenopausal vaginal bleeding]], [[pelvic pain]], and [[vaginal discharge]]. Mixed Mullerian tumors are rare, and they only account for 3 to 4% of all uterine malignancies. The estimated prevalence of mixed Mullerian tumor is 3 cases per 100,000 women in the United States. The diagnosis of mixed Mullerian tumor is made with biopsy. Biopsy findings of mixed Mullerian tumor, include: tumor with carcinomatous and sarcoma-like elements and angiolymphatic invasion. Surgery is the mainstay of therapy for mixed Mullerian tumor. Total hysterectomy in conjunction with surgical staging is the most common approach to the treatment of mixed Mullerian tumor. Prognosis is generally poor, and the 5-year survival rate of patients with mixed Mullerian tumor is approximately 33% to 39%.<ref name="pmid9656116">{{cite journal |vauthors=Clement PB, Zubovits JT, Young RH, Scully RE |title=Malignant mullerian mixed tumors of the uterine cervix: a report of nine cases of a neoplasm with morphology often different from its counterpart in the corpus |journal=Int. J. Gynecol. Pathol. |volume=17 |issue=3 |pages=211–22 |year=1998 |pmid=9656116 |doi= |url=}}</ref>

==Historical Perspective==
*Mixed Mullerian tumor was first described by Ferriera and colleagues in 1951.<ref name="pmid16051326">{{cite journal |vauthors=Wright JD, Rosenblum K, Huettner PC, Mutch DG, Rader JS, Powell MA, Gibb RK |title=Cervical sarcomas: an analysis of incidence and outcome |journal=Gynecol. Oncol. |volume=99 |issue=2 |pages=348–51 |year=2005 |pmid=16051326 |doi=10.1016/j.ygyno.2005.06.021 |url=}}</ref>

==Classification==
*Mixed Mullerian tumors are normally composed of both carcinomatous (epithelial) and sarcomatous (mesodermal) components.
*Mixed Mullerian tumor may be classified according to pathology findings into 2 types:
'''Epitheloid subtype'''
:*[[Adenocarcinoma - endometrium|Endometroid adenocarcinoma]] (most common)
:*[[Clear cell tumor|Clear cell carcinoma]]
:*[[Mucinous carcinoma]]
:*Papillary-serous carcinoma
'''Sarcomatoid subtype'''
:*Undifferentiated sarcoma
:*[[Rhabdomyosarcoma]]

*Mixed Mullerian tumor may also be classified according to anatomical location into 7 types:
:*[[Uterine corpus cancer|Uterine corpus]]
:*[[Cervix]]
:*[[Ovaries]]
:*[[Fallopian tubes]]
:*Vagina
:*[[Peritoneum]]
:*Extragenital sites

==Pathophysiology==
*The pathogenesis of mixed Mullerian tumor is characterized by epithelial and stromal growth, and the transdifferentiation of uterine carcinoma into sarcoma.<ref name="pato">D'Angelo E, Prat J. Pathology of mixed Mullerian tumours. Best Pract Res Clin Obstet Gynaecol. 2011;25:705-718.</ref>
*The PIK3CA gene has been associated with the development of mixed Mullerian tumor, involving the PI3K pathway.
*Genes involved in the pathogenesis of mixed Mullerian tumor, include: <ref name="MMM">Mutation Profiling in Uterine Carcinosarcoma / Malignant Mixed Mullerian Tumors. Melissa McConechy; David Huntsman, MD. ESUN. http://sarcomahelp.org/carcinosarcoma.html Accessed on April 7, 2016</ref>
:*PIK3CA (50% of the tumors)
:*[[PTEN gene|PTEN]] (30% of the tumors)
:*PIK3R1 (30% of the tumors)
*On gross pathology, a large cervical mass is a characteristic finding of mixed Mullerian tumor.
*On microscopic histopathological analysis, high-grade stromal sarcoma, poorly differentiated epithelial cells, and angiolymphatic invasion are characteristic findings of mixed Mullerian tumor.<ref name="pmid16813659">{{cite journal |vauthors=Maheshwari A, Gupta S, Shet T, Wuntkal R, Tongaonkar HB |title=Diagnostic dilemma in a case of malignant mixed mullerian tumor of the cervix |journal=World J Surg Oncol |volume=4 |issue= |pages=36 |year=2006 |pmid=16813659 |pmc=1526432 |doi=10.1186/1477-7819-4-36 |url=}}</ref>

==Causes==
*The most important cause of mixed Mullerian tumors is the mutation in genes PTEN, ARID1A, PIK3R1, and POLE.<ref name="MMM">Wada H, Enomoto T, Fujita M, et al. Molecular evidence that most but not all carcinosarcomas of the uterus are combination tumors. Cancer Res. 1997;57:5379-5385.</ref>
*Mixed Mullerian tumor may also be caused by chronic estrogen stimulation.

==Differentiating Mixed Mullerian tumor from other Diseases==
*Mixed Mullerian tumor must be differentiated from other diseases that cause abnormal vaginal bleeding, abdominal pain, and uterus enlargement such as:
:*[[Leiomyosarcoma|Uterine leiomyosarcoma]]
:*[[Adenocarcinoma - endometrium|Adenocarcinoma of the uterus]]
:*[[Endometrial cancer differential diagnosis|Endometrial cancer]]

==Epidemiology and Demographics==
* Mixed Mullerian tumor is rare, it only accounts for 3 to 4% of all uterine malignancies.<ref name="pmid15047237">{{cite journal |vauthors=Brooks SE, Zhan M, Cote T, Baquet CR |title=Surveillance, epidemiology, and end results analysis of 2677 cases of uterine sarcoma 1989-1999 |journal=Gynecol. Oncol. |volume=93 |issue=1 |pages=204–8 |year=2004 |pmid=15047237 |doi=10.1016/j.ygyno.2003.12.029 |url=}}</ref>
* The estimated prevalence of mixed Mullerian tumor is 3 cases per 100,000 women in the United States.<ref name="pmid15047237">{{cite journal |vauthors=Brooks SE, Zhan M, Cote T, Baquet CR |title=Surveillance, epidemiology, and end results analysis of 2677 cases of uterine sarcoma 1989-1999 |journal=Gynecol. Oncol. |volume=93 |issue=1 |pages=204–8 |year=2004 |pmid=15047237 |doi=10.1016/j.ygyno.2003.12.029 |url=}}</ref>
===Age===
*The median age at diagnosis of Mixed Mullerian tumor is 66 years
*Mixed Mullerian tumor is more commonly observed among patients aged between 50 and 60 years old.
*Mixed Mullerian tumor is more commonly observed among postmenopausal women
===Race===
*There is no racial predilection for mixed Mullerian tumor.<ref name="pmid15047237">{{cite journal |vauthors=Brooks SE, Zhan M, Cote T, Baquet CR |title=Surveillance, epidemiology, and end results analysis of 2677 cases of uterine sarcoma 1989-1999 |journal=Gynecol. Oncol. |volume=93 |issue=1 |pages=204–8 |year=2004 |pmid=15047237 |doi=10.1016/j.ygyno.2003.12.029 |url=}}</ref>

==Risk Factors==
*Common risk factors in the development of mixed Mullerian tumor are [[Radiation|exposure to radiation]], [[Estrogen|excessive estrogen exposure]], [[obesity]], and nulliparity.<ref name="pmid20642852">{{cite journal |vauthors=Kanthan R, Senger JL, Diudea D |title=Malignant mixed Mullerian tumors of the uterus: histopathological evaluation of cell cycle and apoptotic regulatory proteins |journal=World J Surg Oncol |volume=8 |issue= |pages=60 |year=2010 |pmid=20642852 |pmc=2913917 |doi=10.1186/1477-7819-8-60 |url=}}</ref>

== Natural History, Complications and Prognosis==
*Early clinical features include [[Vaginal bleeding|postmenopausal vaginal bleeding]], [[pelvic pain]], and [[vaginal discharge]].
*If left untreated, the majority of patients with mixed Mullerian tumor may progress quickly to develop lymph node invasion, [[metastasis]], and death.
*Prognosis is generally poor, and the 5-year survival rate of patients with Mixed Mullerian tumor is approximately 33% to 39%.
*Findings associated with good prognosis include p16 and Mcl-1 gene expression.<ref name="pmid16813659">{{cite journal |vauthors=Maheshwari A, Gupta S, Shet T, Wuntkal R, Tongaonkar HB |title=Diagnostic dilemma in a case of malignant mixed mullerian tumor of the cervix |journal=World J Surg Oncol |volume=4 |issue= |pages=36 |year=2006 |pmid=16813659 |pmc=1526432 |doi=10.1186/1477-7819-4-36 |url=}}</ref>

== Diagnosis ==
===Diagnostic Criteria===
*The diagnosis of mixed Mullerian tumor is made with biopsy.
*Biopsy findings of mixed Mullerian tumor, include:<ref name="pmid9656116">{{cite journal |vauthors=Clement PB, Zubovits JT, Young RH, Scully RE |title=Malignant mullerian mixed tumors of the uterine cervix: a report of nine cases of a neoplasm with morphology often different from its counterpart in the corpus |journal=Int. J. Gynecol. Pathol. |volume=17 |issue=3 |pages=211–22 |year=1998 |pmid=9656116 |doi= |url=}}</ref>
:*Tumor with carcinomatous and sarcoma-like elements
:*Angiolymphatic invasion

=== Symptoms ===
*Mixed Mullerian tumor may be initially asymptomatic.
*Symptoms of mixed Mullerian tumor may include the following:<ref name="pmid20642852">{{cite journal |vauthors=Kanthan R, Senger JL, Diudea D |title=Malignant mixed Mullerian tumors of the uterus: histopathological evaluation of cell cycle and apoptotic regulatory proteins |journal=World J Surg Oncol |volume=8 |issue= |pages=60 |year=2010 |pmid=20642852 |pmc=2913917 |doi=10.1186/1477-7819-8-60 |url=}}</ref>
*Early symptoms
:* Abnormal [[vaginal bleeding]], abnormal menstrual periods
:* [[Metrorrhagia]] in premenopausal women
:* Postmenopausal [[vaginal bleeding]] <ref name="pmid22513918">{{cite journal| author=Kong A, Johnson N, Kitchener HC, Lawrie TA| title=Adjuvant radiotherapy for stage I endometrial cancer. | journal=Cochrane Database Syst Rev | year= 2012 | volume= 4 | issue= | pages= CD003916 | pmid=22513918 | doi=10.1002/14651858.CD003916.pub4 | pmc=PMC4164955 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22513918 }} </ref>
:* Postcoital bleeding
*Advanced symptoms
:* [[Polyuria]] and [[dysuria]], If a tumor places pressure on the bladder or urethra
:* [[Pelvic pain]] and [[dyspareunia]]
:* [[Fatigue]] and unexplained [[weight loss]]

=== Physical Examination ===
*Patients with mixed Mullerian tumor may have a normal appearance.
*Pelvic examination may be remarkable for:<ref name="pmid9656116">{{cite journal |vauthors=Clement PB, Zubovits JT, Young RH, Scully RE |title=Malignant mullerian mixed tumors of the uterine cervix: a report of nine cases of a neoplasm with morphology often different from its counterpart in the corpus |journal=Int. J. Gynecol. Pathol. |volume=17 |issue=3 |pages=211–22 |year=1998 |pmid=9656116 |doi= |url=}}</ref>
:*[[Vaginal bleeding]]
:*[[Enlarged uterus]] (advanced stage)

=== Laboratory Findings ===
*Laboratory findings associated with mixed Mullerian tumor, may include:
:*Anemia
:*Elevated CA-125

===Imaging Findings===
*Enhanced CT scan and MRI is the imaging modalities of choice for mixed Mullerian tumor.
*On MRI, findings of mixed Mullerian tumor, may include:<ref name="pmid4705156">{{cite journal |vauthors=Abell MR, Ramirez JA |title=Sarcomas and carcinosarcomas of the uterine cervix |journal=Cancer |volume=31 |issue=5 |pages=1176–92 |year=1973 |pmid=4705156 |doi= |url=}}</ref>
:*T1: predominantly isointense to both myometrium (75%) and endometrium (70%)
:*T2: hyper-intense to myometrium (90%) either hypo-intense (55%) or isointense (41%) to endometrium.
*On enhanced CT, findings of mixed Mullerian tumor, may include:
:*Heterogeneously hypodense and ill defined mass
:*Dilatation of uterine cavity
====Gallery====
<gallery>
Image:Malignant mixed mullerian tumor 001.jpg|
Image:Malignant mixed mullerian tumor 002.jpg|
Image:Malignant mixed mullerian tumor 003.jpg|
Image:Malignant mixed mullerian tumor 004.jpg|
</gallery>

=== Other Diagnostic Studies ===
*Mixed Mullerian tumor may also be diagnosed using [[laparoscopy]], and FDG PET/CT.

== Treatment ==
=== Medical Therapy ===
*There is no treatment for mixed Mullerian tumor; the mainstay of therapy is supportive care.
*The medical management for mixed Mullerian tumor, include:<ref name="pmid4705156">{{cite journal |vauthors=Abell MR, Ramirez JA |title=Sarcomas and carcinosarcomas of the uterine cervix |journal=Cancer |volume=31 |issue=5 |pages=1176–92 |year=1973 |pmid=4705156 |doi= |url=}}</ref>
:*[[Chemotherapy]] [[ifosfamide]]-based regimen
:*[[Radiotherapy]] (vaginal brachytherapy)
:*Chemotherapy plus radiation therapy

=== Surgery ===
*Surgery is the mainstay of therapy for mixed Mullerian tumor.
*Total hysterectomy in conjunction with surgical staging is the most common approach to the treatment of mixed Mullerian tumor.
*Different surgical procedures for the treatment of mixed Mullerian tumor, include:<ref name="pmid4705156">{{cite journal |vauthors=Abell MR, Ramirez JA |title=Sarcomas and carcinosarcomas of the uterine cervix |journal=Cancer |volume=31 |issue=5 |pages=1176–92 |year=1973 |pmid=4705156 |doi= |url=}}</ref>
:*[[Hysterectomy|Total hysterectomy]]
:*Bilateral salpingo-oophorectomy
:*Pelvic and para-aortic lymph node dissection
:*Cytology of peritoneal washings
:*Omentectomy
:*Biopsies of peritoneal surfaces

=== Prevention ===
*There are no primary preventive measures available for mixed Mullerian tumor.
*Once diagnosed and successfully treated, patients with mixed Mullerian tumor are followed-up every 6 or 12 months.
*Follow-up testing include pelvic examination, ultrasound, and biomarker monitorization.

==References==
{{Reflist|2}}

[[Category: Oncology]]

Mixed mullerian tumor

2016-04-22T14:59:26Z

Sergekorjian: /* Overview */

__NOTOC__
{{SI}}
{{CMG}} {{AE}} {{MV}}

{{SK}} Mixed Müllerian tumor; MMMT; Malignant mixed Müllerian tumor; Carcinosarcoma of the uterus; Sarcomatoid carcinoma of the uterus; Malignant mesodermal mixed tumor; Metaplastic carcinoma

==Overview==

'''Malignant Mixed Mullerian tumor''' (MMMT) is a rare [[uterine sarcoma]] or carcinosarcoma. Mixed Mullerian tumors are normally composed of both carcinomatous (epithelial) and sarcomatous (mesodermal) components. Mixed Mullerian tumor may be classified according to pathology findings into 2 types: epitheloid subtype and sarcomatoid subtype. Mixed Mullerian tumor may also be classified according to anatomical location into 7 types: [[Uterine corpus cancer|uterine corpus]], [[cervix]], [[ovaries]], [[fallopian tubes]], [[Vaginal Cancer|vagina]], [[peritoneum]], and extragenital sites. Common risk factors in the development of mixed Mullerian tumor are [[Radiation|exposure to radiation]], [[Estrogen|excessive estrogen exposure]], [[obesity]], and nulliparity.<ref name="pmid20642852">{{cite journal |vauthors=Kanthan R, Senger JL, Diudea D |title=Malignant mixed Mullerian tumors of the uterus: histopathological evaluation of cell cycle and apoptotic regulatory proteins |journal=World J Surg Oncol |volume=8 |issue= |pages=60 |year=2010 |pmid=20642852 |pmc=2913917 |doi=10.1186/1477-7819-8-60 |url=}}</ref> Mixed Mullerian tumor is more commonly observed among postmenopausal women between 50 and 60 years old. Early clinical features include [[Vaginal bleeding|postmenopausal vaginal bleeding]], [[pelvic pain]], and [[vaginal discharge]]. Mixed Mullerian tumors are rare, and they only account for 3 to 4% of all uterine malignancies. The estimated prevalence of mixed Mullerian tumor is 3 cases per 100,000 women in the United States. The diagnosis of mixed Mullerian tumor is made with biopsy. Biopsy findings of mixed Mullerian tumor, include: tumor with carcinomatous and sarcoma-like elements and angiolymphatic invasion. Surgery is the mainstay of therapy for mixed Mullerian tumor. Total hysterectomy in conjunction with surgical staging is the most common approach to the treatment of mixed Mullerian tumor. Prognosis is generally poor, and the 5-year survival rate of patients with mixed Mullerian tumor is approximately 33% to 39%.<ref name="pmid9656116">{{cite journal |vauthors=Clement PB, Zubovits JT, Young RH, Scully RE |title=Malignant mullerian mixed tumors of the uterine cervix: a report of nine cases of a neoplasm with morphology often different from its counterpart in the corpus |journal=Int. J. Gynecol. Pathol. |volume=17 |issue=3 |pages=211–22 |year=1998 |pmid=9656116 |doi= |url=}}</ref>

==Historical Perspective==
*Mixed Mullerian tumor was first described by Ferriera and colleagues in 1951.<ref name="pmid16051326">{{cite journal |vauthors=Wright JD, Rosenblum K, Huettner PC, Mutch DG, Rader JS, Powell MA, Gibb RK |title=Cervical sarcomas: an analysis of incidence and outcome |journal=Gynecol. Oncol. |volume=99 |issue=2 |pages=348–51 |year=2005 |pmid=16051326 |doi=10.1016/j.ygyno.2005.06.021 |url=}}</ref>

==Classification==
*Mixed Mullerian tumors are normally composed of both carcinomatous (epithelial) and sarcomatous (mesodermal) components.
*Mixed Mullerian tumor may be classified according to pathology findings into 2 types:
'''Epitheloid subtype'''
:*[[Adenocarcinoma - endometrium|Endometroid adenocarcinoma]] (most common)
:*[[Clear cell tumor|Clear cell carcinoma]]
:*[[Mucinous carcinoma]]
:*Papillary-serous carcinoma
'''Sarcomatoid subtype'''
:*Undifferentiated sarcoma
:*[[Rhabdomyosarcoma]]

*Mixed Mullerian tumor may also be classified according to anatomical location into 7 types:
:*[[Uterine corpus cancer|Uterine corpus]]
:*[[Cervix]]
:*[[Ovaries]]
:*[[Fallopian tubes]]
:*Vagina
:*[[Peritoneum]]
:*Extragenital sites

==Pathophysiology==
*The pathogenesis of mixed Mullerian tumor is characterized by epithelial and stromal growth, and the transdifferentiation of uterine carcinoma into sarcoma.<ref name="pato">D'Angelo E, Prat J. Pathology of mixed Mullerian tumours. Best Pract Res Clin Obstet Gynaecol. 2011;25:705-718.</ref>
*The PIK3CA gene has been associated with the development of mixed Mullerian tumor, involving the PI3K pathway.
*Genes involved in the pathogenesis of mixed Mullerian tumor, include: <ref name="MMM">Mutation Profiling in Uterine Carcinosarcoma / Malignant Mixed Mullerian Tumors. Melissa McConechy; David Huntsman, MD. ESUN. http://sarcomahelp.org/carcinosarcoma.html Accessed on April 7, 2016</ref>
:*PIK3CA (50% of the tumors)
:*[[PTEN gene|PTEN]] (30% of the tumors)
:*PIK3R1 (30% of the tumors)
*On gross pathology, a large cervical mass is a characteristic finding of mixed Mullerian tumor.
*On microscopic histopathological analysis, high-grade stromal sarcoma, poorly differentiated epithelial cells, and angiolymphatic invasion are characteristic findings of mixed Mullerian tumor.<ref name="pmid16813659">{{cite journal |vauthors=Maheshwari A, Gupta S, Shet T, Wuntkal R, Tongaonkar HB |title=Diagnostic dilemma in a case of malignant mixed mullerian tumor of the cervix |journal=World J Surg Oncol |volume=4 |issue= |pages=36 |year=2006 |pmid=16813659 |pmc=1526432 |doi=10.1186/1477-7819-4-36 |url=}}</ref>

==Causes==
*The most important cause of mixed Mullerian tumors is the mutation in genes PTEN, ARID1A, PIK3R1, and POLE.<ref name="MMM">Wada H, Enomoto T, Fujita M, et al. Molecular evidence that most but not all carcinosarcomas of the uterus are combination tumors. Cancer Res. 1997;57:5379-5385.</ref>
*Mixed Mullerian tumor may also be caused by chronic estrogen stimulation.

==Differentiating Mixed Mullerian tumor from other Diseases==
*Mixed Mullerian tumor must be differentiated from other diseases that cause abnormal vaginal bleeding, abdominal pain, and uterus enlargement such as:
:*[[Leiomyosarcoma|Uterine leiomyosarcoma]]
:*[[Adenocarcinoma - endometrium|Adenocarcinoma of the uterus]]
:*[[Endometrial cancer differential diagnosis|Endometrial cancer]]

==Epidemiology and Demographics==
* Mixed Mullerian tumor is rare, it only accounts for 3 to 4% of all uterine malignancies.<ref name="pmid15047237">{{cite journal |vauthors=Brooks SE, Zhan M, Cote T, Baquet CR |title=Surveillance, epidemiology, and end results analysis of 2677 cases of uterine sarcoma 1989-1999 |journal=Gynecol. Oncol. |volume=93 |issue=1 |pages=204–8 |year=2004 |pmid=15047237 |doi=10.1016/j.ygyno.2003.12.029 |url=}}</ref>
* The estimated prevalence of mixed Mullerian tumor is 3 cases per 100,000 women in the United States.<ref name="pmid15047237">{{cite journal |vauthors=Brooks SE, Zhan M, Cote T, Baquet CR |title=Surveillance, epidemiology, and end results analysis of 2677 cases of uterine sarcoma 1989-1999 |journal=Gynecol. Oncol. |volume=93 |issue=1 |pages=204–8 |year=2004 |pmid=15047237 |doi=10.1016/j.ygyno.2003.12.029 |url=}}</ref>
===Age===
*The median age at diagnosis of Mixed Mullerian tumor is 66 years
*Mixed Mullerian tumor is more commonly observed among patients aged between 50 and 60 years old.
*Mixed Mullerian tumor is more commonly observed among postmenopausal women
===Race===
*There is no racial predilection for mixed Mullerian tumor.<ref name="pmid15047237">{{cite journal |vauthors=Brooks SE, Zhan M, Cote T, Baquet CR |title=Surveillance, epidemiology, and end results analysis of 2677 cases of uterine sarcoma 1989-1999 |journal=Gynecol. Oncol. |volume=93 |issue=1 |pages=204–8 |year=2004 |pmid=15047237 |doi=10.1016/j.ygyno.2003.12.029 |url=}}</ref>

==Risk Factors==
*Common risk factors in the development of mixed Mullerian tumor are [[Radiation|exposure to radiation]], [[Estrogen|excessive estrogen exposure]], [[obesity]], and nulliparity.<ref name="pmid20642852">{{cite journal |vauthors=Kanthan R, Senger JL, Diudea D |title=Malignant mixed Mullerian tumors of the uterus: histopathological evaluation of cell cycle and apoptotic regulatory proteins |journal=World J Surg Oncol |volume=8 |issue= |pages=60 |year=2010 |pmid=20642852 |pmc=2913917 |doi=10.1186/1477-7819-8-60 |url=}}</ref>

== Natural History, Complications and Prognosis==
*Early clinical features include [[Vaginal bleeding|postmenopausal vaginal bleeding]], [[pelvic pain]], and [[vaginal discharge]].
*If left untreated, the majority of patients with mixed Mullerian tumor may progress quickly to develop lymph node invasion, [[metastasis]], and death.
*Prognosis is generally poor, and the 5-year survival rate of patients with Mixed Mullerian tumor is approximately 33% to 39%.
*Findings associated with good prognosis include p16 and Mcl-1 gene expression.<ref name="pmid16813659">{{cite journal |vauthors=Maheshwari A, Gupta S, Shet T, Wuntkal R, Tongaonkar HB |title=Diagnostic dilemma in a case of malignant mixed mullerian tumor of the cervix |journal=World J Surg Oncol |volume=4 |issue= |pages=36 |year=2006 |pmid=16813659 |pmc=1526432 |doi=10.1186/1477-7819-4-36 |url=}}</ref>

== Diagnosis ==
===Diagnostic Criteria===
*The diagnosis of mixed Mullerian tumor is made with biopsy.
*Biopsy findings of mixed Mullerian tumor, include:<ref name="pmid9656116">{{cite journal |vauthors=Clement PB, Zubovits JT, Young RH, Scully RE |title=Malignant mullerian mixed tumors of the uterine cervix: a report of nine cases of a neoplasm with morphology often different from its counterpart in the corpus |journal=Int. J. Gynecol. Pathol. |volume=17 |issue=3 |pages=211–22 |year=1998 |pmid=9656116 |doi= |url=}}</ref>
:*Tumor with carcinomatous and sarcoma-like elements
:*Angiolymphatic invasion

=== Symptoms ===
*Mixed Mullerian tumor may be initially asymptomatic.
*Symptoms of mixed Mullerian tumor may include the following:<ref name="pmid20642852">{{cite journal |vauthors=Kanthan R, Senger JL, Diudea D |title=Malignant mixed Mullerian tumors of the uterus: histopathological evaluation of cell cycle and apoptotic regulatory proteins |journal=World J Surg Oncol |volume=8 |issue= |pages=60 |year=2010 |pmid=20642852 |pmc=2913917 |doi=10.1186/1477-7819-8-60 |url=}}</ref>
*Early symptoms
:* Abnormal [[vaginal bleeding]], abnormal menstrual periods
:* [[Metrorrhagia]] in premenopausal women
:* Postmenopausal [[vaginal bleeding]] <ref name="pmid22513918">{{cite journal| author=Kong A, Johnson N, Kitchener HC, Lawrie TA| title=Adjuvant radiotherapy for stage I endometrial cancer. | journal=Cochrane Database Syst Rev | year= 2012 | volume= 4 | issue= | pages= CD003916 | pmid=22513918 | doi=10.1002/14651858.CD003916.pub4 | pmc=PMC4164955 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22513918 }} </ref>
:* Postcoital bleeding
*Advanced symptoms
:* [[Polyuria]] and [[dysuria]], If a tumor places pressure on the bladder or urethra
:* [[Pelvic pain]] and [[dyspareunia]]
:* [[Fatigue]] and unexplained [[weight loss]]

=== Physical Examination ===
*Patients with mixed Mullerian tumor may have a normal appearance.
*Pelvic examination may be remarkable for:<ref name="pmid9656116">{{cite journal |vauthors=Clement PB, Zubovits JT, Young RH, Scully RE |title=Malignant mullerian mixed tumors of the uterine cervix: a report of nine cases of a neoplasm with morphology often different from its counterpart in the corpus |journal=Int. J. Gynecol. Pathol. |volume=17 |issue=3 |pages=211–22 |year=1998 |pmid=9656116 |doi= |url=}}</ref>
:*[[Vaginal bleeding]]
:*[[Enlarged uterus]] (advanced stage)

=== Laboratory Findings ===
*Laboratory findings associated with mixed Mullerian tumor, may include:
:*Anemia
:*Elevated CA-125

===Imaging Findings===
*Enhanced CT scan and MRI is the imaging modalities of choice for mixed Mullerian tumor.
*On MRI, findings of mixed Mullerian tumor, may include:<ref name="pmid4705156">{{cite journal |vauthors=Abell MR, Ramirez JA |title=Sarcomas and carcinosarcomas of the uterine cervix |journal=Cancer |volume=31 |issue=5 |pages=1176–92 |year=1973 |pmid=4705156 |doi= |url=}}</ref>
:*T1: predominantly isointense to both myometrium (75%) and endometrium (70%)
:*T2: hyper-intense to myometrium (90%) either hypo-intense (55%) or isointense (41%) to endometrium.
*On enhanced CT, findings of mixed Mullerian tumor, may include:
:*Heterogeneously hypodense and ill defined mass
:*Dilatation of uterine cavity
====Gallery====
<gallery>
Image:Malignant mixed mullerian tumor 001.jpg|
Image:Malignant mixed mullerian tumor 002.jpg|
Image:Malignant mixed mullerian tumor 003.jpg|
Image:Malignant mixed mullerian tumor 004.jpg|
</gallery>

=== Other Diagnostic Studies ===
*Mixed Mullerian tumor may also be diagnosed using [[laparoscopy]], and FDG PET/CT.

== Treatment ==
=== Medical Therapy ===
*There is no treatment for mixed Mullerian tumor; the mainstay of therapy is supportive care.
*The medical management for mixed Mullerian tumor, include:<ref name="pmid4705156">{{cite journal |vauthors=Abell MR, Ramirez JA |title=Sarcomas and carcinosarcomas of the uterine cervix |journal=Cancer |volume=31 |issue=5 |pages=1176–92 |year=1973 |pmid=4705156 |doi= |url=}}</ref>
:*[[Chemotherapy]] [[ifosfamide]]-based regimen
:*[[Radiotherapy]] (vaginal brachytherapy)
:*Chemotherapy plus radiation therapy

=== Surgery ===
*Surgery is the mainstay of therapy for mixed Mullerian tumor.
*Total hysterectomy in conjunction with surgical staging is the most common approach to the treatment of mixed Mullerian tumor.
*Different surgical procedures for the treatment of mixed Mullerian tumor, include:<ref name="pmid4705156">{{cite journal |vauthors=Abell MR, Ramirez JA |title=Sarcomas and carcinosarcomas of the uterine cervix |journal=Cancer |volume=31 |issue=5 |pages=1176–92 |year=1973 |pmid=4705156 |doi= |url=}}</ref>
:*[[Hysterectomy|Total hysterectomy]]
:*Bilateral salpingo-oophorectomy
:*Pelvic and para-aortic lymph node dissection
:*Cytology of peritoneal washings
:*Omentectomy
:*Biopsies of peritoneal surfaces

=== Prevention ===
*There are no primary preventive measures available for mixed Mullerian tumor.
*Once diagnosed and successfully treated, patients with mixed Mullerian tumor are followed-up every 6 or 12 months.
*Follow-up testing include pelvic examination, ultrasound, and biomarker monitorization.

==References==
{{Reflist|2}}

[[Category: Oncology]]

Mixed Mullerian tumor

2016-04-22T14:56:19Z

Sergekorjian: Sergekorjian moved page Mixed Mullerian tumor to Mixed mullerian tumor

#REDIRECT [[Mixed mullerian tumor]]

Mixed mullerian tumor

2016-04-22T14:56:07Z

Sergekorjian: Sergekorjian moved page Mixed Mullerian tumor to Mixed mullerian tumor

__NOTOC__
{{SI}}
{{CMG}} {{AE}} {{MV}}

{{SK}} Mixed Müllerian tumor; MMMT; Malignant mixed Müllerian tumor; Carcinosarcoma of the uterus; Sarcomatoid carcinoma of the uterus; Malignant mesodermal mixed tumor; Metaplastic carcinoma

==Overview==

'''Mixed Mullerian tumor''' (MMMT) is a rare [[uterine sarcoma]] or carcinosarcoma. Mixed Mullerian tumors are normally composed of both carcinomatous (epithelial) and sarcomatous (mesodermal) components. Mixed Mullerian tumor may be classified according to pathology findings into 2 types: epitheloid subtype and sarcomatoid subtype. Mixed Mullerian tumor may also be classified according to anatomical location into 7 types: [[Uterine corpus cancer|uterine corpus]], [[cervix]], [[ovaries]], [[fallopian tubes]], [[Vaginal Cancer|vagina]], [[peritoneum]], and extragenital sites. Common risk factors in the development of mixed Mullerian tumor are [[Radiation|exposure to radiation]], [[Estrogen|excessive estrogen exposure]], [[obesity]], and nulliparity.<ref name="pmid20642852">{{cite journal |vauthors=Kanthan R, Senger JL, Diudea D |title=Malignant mixed Mullerian tumors of the uterus: histopathological evaluation of cell cycle and apoptotic regulatory proteins |journal=World J Surg Oncol |volume=8 |issue= |pages=60 |year=2010 |pmid=20642852 |pmc=2913917 |doi=10.1186/1477-7819-8-60 |url=}}</ref> Mixed Mullerian tumor is more commonly observed among postmenopausal women between 50 and 60 years old. Early clinical features include [[Vaginal bleeding|postmenopausal vaginal bleeding]], [[pelvic pain]], and [[vaginal discharge]]. Mixed Mullerian tumors are rare, and they only account for 3 to 4% of all uterine malignancies. The estimated prevalence of mixed Mullerian tumor is 3 cases per 100,000 women in the United States. The diagnosis of mixed Mullerian tumor is made with biopsy. Biopsy findings of mixed Mullerian tumor, include: tumor with carcinomatous and sarcoma-like elements and angiolymphatic invasion. Surgery is the mainstay of therapy for mixed Mullerian tumor. Total hysterectomy in conjunction with surgical staging is the most common approach to the treatment of mixed Mullerian tumor. Prognosis is generally poor, and the 5-year survival rate of patients with mixed Mullerian tumor is approximately 33% to 39%.<ref name="pmid9656116">{{cite journal |vauthors=Clement PB, Zubovits JT, Young RH, Scully RE |title=Malignant mullerian mixed tumors of the uterine cervix: a report of nine cases of a neoplasm with morphology often different from its counterpart in the corpus |journal=Int. J. Gynecol. Pathol. |volume=17 |issue=3 |pages=211–22 |year=1998 |pmid=9656116 |doi= |url=}}</ref>

==Historical Perspective==
*Mixed Mullerian tumor was first described by Ferriera and colleagues in 1951.<ref name="pmid16051326">{{cite journal |vauthors=Wright JD, Rosenblum K, Huettner PC, Mutch DG, Rader JS, Powell MA, Gibb RK |title=Cervical sarcomas: an analysis of incidence and outcome |journal=Gynecol. Oncol. |volume=99 |issue=2 |pages=348–51 |year=2005 |pmid=16051326 |doi=10.1016/j.ygyno.2005.06.021 |url=}}</ref>

==Classification==
*Mixed Mullerian tumors are normally composed of both carcinomatous (epithelial) and sarcomatous (mesodermal) components.
*Mixed Mullerian tumor may be classified according to pathology findings into 2 types:
'''Epitheloid subtype'''
:*[[Adenocarcinoma - endometrium|Endometroid adenocarcinoma]] (most common)
:*[[Clear cell tumor|Clear cell carcinoma]]
:*[[Mucinous carcinoma]]
:*Papillary-serous carcinoma
'''Sarcomatoid subtype'''
:*Undifferentiated sarcoma
:*[[Rhabdomyosarcoma]]

*Mixed Mullerian tumor may also be classified according to anatomical location into 7 types:
:*[[Uterine corpus cancer|Uterine corpus]]
:*[[Cervix]]
:*[[Ovaries]]
:*[[Fallopian tubes]]
:*Vagina
:*[[Peritoneum]]
:*Extragenital sites

==Pathophysiology==
*The pathogenesis of mixed Mullerian tumor is characterized by epithelial and stromal growth, and the transdifferentiation of uterine carcinoma into sarcoma.<ref name="pato">D'Angelo E, Prat J. Pathology of mixed Mullerian tumours. Best Pract Res Clin Obstet Gynaecol. 2011;25:705-718.</ref>
*The PIK3CA gene has been associated with the development of mixed Mullerian tumor, involving the PI3K pathway.
*Genes involved in the pathogenesis of mixed Mullerian tumor, include: <ref name="MMM">Mutation Profiling in Uterine Carcinosarcoma / Malignant Mixed Mullerian Tumors. Melissa McConechy; David Huntsman, MD. ESUN. http://sarcomahelp.org/carcinosarcoma.html Accessed on April 7, 2016</ref>
:*PIK3CA (50% of the tumors)
:*[[PTEN gene|PTEN]] (30% of the tumors)
:*PIK3R1 (30% of the tumors)
*On gross pathology, a large cervical mass is a characteristic finding of mixed Mullerian tumor.
*On microscopic histopathological analysis, high-grade stromal sarcoma, poorly differentiated epithelial cells, and angiolymphatic invasion are characteristic findings of mixed Mullerian tumor.<ref name="pmid16813659">{{cite journal |vauthors=Maheshwari A, Gupta S, Shet T, Wuntkal R, Tongaonkar HB |title=Diagnostic dilemma in a case of malignant mixed mullerian tumor of the cervix |journal=World J Surg Oncol |volume=4 |issue= |pages=36 |year=2006 |pmid=16813659 |pmc=1526432 |doi=10.1186/1477-7819-4-36 |url=}}</ref>

==Causes==
*The most important cause of mixed Mullerian tumors is the mutation in genes PTEN, ARID1A, PIK3R1, and POLE.<ref name="MMM">Wada H, Enomoto T, Fujita M, et al. Molecular evidence that most but not all carcinosarcomas of the uterus are combination tumors. Cancer Res. 1997;57:5379-5385.</ref>
*Mixed Mullerian tumor may also be caused by chronic estrogen stimulation.

==Differentiating Mixed Mullerian tumor from other Diseases==
*Mixed Mullerian tumor must be differentiated from other diseases that cause abnormal vaginal bleeding, abdominal pain, and uterus enlargement such as:
:*[[Leiomyosarcoma|Uterine leiomyosarcoma]]
:*[[Adenocarcinoma - endometrium|Adenocarcinoma of the uterus]]
:*[[Endometrial cancer differential diagnosis|Endometrial cancer]]

==Epidemiology and Demographics==
* Mixed Mullerian tumor is rare, it only accounts for 3 to 4% of all uterine malignancies.<ref name="pmid15047237">{{cite journal |vauthors=Brooks SE, Zhan M, Cote T, Baquet CR |title=Surveillance, epidemiology, and end results analysis of 2677 cases of uterine sarcoma 1989-1999 |journal=Gynecol. Oncol. |volume=93 |issue=1 |pages=204–8 |year=2004 |pmid=15047237 |doi=10.1016/j.ygyno.2003.12.029 |url=}}</ref>
* The estimated prevalence of mixed Mullerian tumor is 3 cases per 100,000 women in the United States.<ref name="pmid15047237">{{cite journal |vauthors=Brooks SE, Zhan M, Cote T, Baquet CR |title=Surveillance, epidemiology, and end results analysis of 2677 cases of uterine sarcoma 1989-1999 |journal=Gynecol. Oncol. |volume=93 |issue=1 |pages=204–8 |year=2004 |pmid=15047237 |doi=10.1016/j.ygyno.2003.12.029 |url=}}</ref>
===Age===
*The median age at diagnosis of Mixed Mullerian tumor is 66 years
*Mixed Mullerian tumor is more commonly observed among patients aged between 50 and 60 years old.
*Mixed Mullerian tumor is more commonly observed among postmenopausal women
===Race===
*There is no racial predilection for mixed Mullerian tumor.<ref name="pmid15047237">{{cite journal |vauthors=Brooks SE, Zhan M, Cote T, Baquet CR |title=Surveillance, epidemiology, and end results analysis of 2677 cases of uterine sarcoma 1989-1999 |journal=Gynecol. Oncol. |volume=93 |issue=1 |pages=204–8 |year=2004 |pmid=15047237 |doi=10.1016/j.ygyno.2003.12.029 |url=}}</ref>

==Risk Factors==
*Common risk factors in the development of mixed Mullerian tumor are [[Radiation|exposure to radiation]], [[Estrogen|excessive estrogen exposure]], [[obesity]], and nulliparity.<ref name="pmid20642852">{{cite journal |vauthors=Kanthan R, Senger JL, Diudea D |title=Malignant mixed Mullerian tumors of the uterus: histopathological evaluation of cell cycle and apoptotic regulatory proteins |journal=World J Surg Oncol |volume=8 |issue= |pages=60 |year=2010 |pmid=20642852 |pmc=2913917 |doi=10.1186/1477-7819-8-60 |url=}}</ref>

== Natural History, Complications and Prognosis==
*Early clinical features include [[Vaginal bleeding|postmenopausal vaginal bleeding]], [[pelvic pain]], and [[vaginal discharge]].
*If left untreated, the majority of patients with mixed Mullerian tumor may progress quickly to develop lymph node invasion, [[metastasis]], and death.
*Prognosis is generally poor, and the 5-year survival rate of patients with Mixed Mullerian tumor is approximately 33% to 39%.
*Findings associated with good prognosis include p16 and Mcl-1 gene expression.<ref name="pmid16813659">{{cite journal |vauthors=Maheshwari A, Gupta S, Shet T, Wuntkal R, Tongaonkar HB |title=Diagnostic dilemma in a case of malignant mixed mullerian tumor of the cervix |journal=World J Surg Oncol |volume=4 |issue= |pages=36 |year=2006 |pmid=16813659 |pmc=1526432 |doi=10.1186/1477-7819-4-36 |url=}}</ref>

== Diagnosis ==
===Diagnostic Criteria===
*The diagnosis of mixed Mullerian tumor is made with biopsy.
*Biopsy findings of mixed Mullerian tumor, include:<ref name="pmid9656116">{{cite journal |vauthors=Clement PB, Zubovits JT, Young RH, Scully RE |title=Malignant mullerian mixed tumors of the uterine cervix: a report of nine cases of a neoplasm with morphology often different from its counterpart in the corpus |journal=Int. J. Gynecol. Pathol. |volume=17 |issue=3 |pages=211–22 |year=1998 |pmid=9656116 |doi= |url=}}</ref>
:*Tumor with carcinomatous and sarcoma-like elements
:*Angiolymphatic invasion

=== Symptoms ===
*Mixed Mullerian tumor may be initially asymptomatic.
*Symptoms of mixed Mullerian tumor may include the following:<ref name="pmid20642852">{{cite journal |vauthors=Kanthan R, Senger JL, Diudea D |title=Malignant mixed Mullerian tumors of the uterus: histopathological evaluation of cell cycle and apoptotic regulatory proteins |journal=World J Surg Oncol |volume=8 |issue= |pages=60 |year=2010 |pmid=20642852 |pmc=2913917 |doi=10.1186/1477-7819-8-60 |url=}}</ref>
*Early symptoms
:* Abnormal [[vaginal bleeding]], abnormal menstrual periods
:* [[Metrorrhagia]] in premenopausal women
:* Postmenopausal [[vaginal bleeding]] <ref name="pmid22513918">{{cite journal| author=Kong A, Johnson N, Kitchener HC, Lawrie TA| title=Adjuvant radiotherapy for stage I endometrial cancer. | journal=Cochrane Database Syst Rev | year= 2012 | volume= 4 | issue= | pages= CD003916 | pmid=22513918 | doi=10.1002/14651858.CD003916.pub4 | pmc=PMC4164955 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22513918 }} </ref>
:* Postcoital bleeding
*Advanced symptoms
:* [[Polyuria]] and [[dysuria]], If a tumor places pressure on the bladder or urethra
:* [[Pelvic pain]] and [[dyspareunia]]
:* [[Fatigue]] and unexplained [[weight loss]]

=== Physical Examination ===
*Patients with mixed Mullerian tumor may have a normal appearance.
*Pelvic examination may be remarkable for:<ref name="pmid9656116">{{cite journal |vauthors=Clement PB, Zubovits JT, Young RH, Scully RE |title=Malignant mullerian mixed tumors of the uterine cervix: a report of nine cases of a neoplasm with morphology often different from its counterpart in the corpus |journal=Int. J. Gynecol. Pathol. |volume=17 |issue=3 |pages=211–22 |year=1998 |pmid=9656116 |doi= |url=}}</ref>
:*[[Vaginal bleeding]]
:*[[Enlarged uterus]] (advanced stage)

=== Laboratory Findings ===
*Laboratory findings associated with mixed Mullerian tumor, may include:
:*Anemia
:*Elevated CA-125

===Imaging Findings===
*Enhanced CT scan and MRI is the imaging modalities of choice for mixed Mullerian tumor.
*On MRI, findings of mixed Mullerian tumor, may include:<ref name="pmid4705156">{{cite journal |vauthors=Abell MR, Ramirez JA |title=Sarcomas and carcinosarcomas of the uterine cervix |journal=Cancer |volume=31 |issue=5 |pages=1176–92 |year=1973 |pmid=4705156 |doi= |url=}}</ref>
:*T1: predominantly isointense to both myometrium (75%) and endometrium (70%)
:*T2: hyper-intense to myometrium (90%) either hypo-intense (55%) or isointense (41%) to endometrium.
*On enhanced CT, findings of mixed Mullerian tumor, may include:
:*Heterogeneously hypodense and ill defined mass
:*Dilatation of uterine cavity
====Gallery====
<gallery>
Image:Malignant mixed mullerian tumor 001.jpg|
Image:Malignant mixed mullerian tumor 002.jpg|
Image:Malignant mixed mullerian tumor 003.jpg|
Image:Malignant mixed mullerian tumor 004.jpg|
</gallery>

=== Other Diagnostic Studies ===
*Mixed Mullerian tumor may also be diagnosed using [[laparoscopy]], and FDG PET/CT.

== Treatment ==
=== Medical Therapy ===
*There is no treatment for mixed Mullerian tumor; the mainstay of therapy is supportive care.
*The medical management for mixed Mullerian tumor, include:<ref name="pmid4705156">{{cite journal |vauthors=Abell MR, Ramirez JA |title=Sarcomas and carcinosarcomas of the uterine cervix |journal=Cancer |volume=31 |issue=5 |pages=1176–92 |year=1973 |pmid=4705156 |doi= |url=}}</ref>
:*[[Chemotherapy]] [[ifosfamide]]-based regimen
:*[[Radiotherapy]] (vaginal brachytherapy)
:*Chemotherapy plus radiation therapy

=== Surgery ===
*Surgery is the mainstay of therapy for mixed Mullerian tumor.
*Total hysterectomy in conjunction with surgical staging is the most common approach to the treatment of mixed Mullerian tumor.
*Different surgical procedures for the treatment of mixed Mullerian tumor, include:<ref name="pmid4705156">{{cite journal |vauthors=Abell MR, Ramirez JA |title=Sarcomas and carcinosarcomas of the uterine cervix |journal=Cancer |volume=31 |issue=5 |pages=1176–92 |year=1973 |pmid=4705156 |doi= |url=}}</ref>
:*[[Hysterectomy|Total hysterectomy]]
:*Bilateral salpingo-oophorectomy
:*Pelvic and para-aortic lymph node dissection
:*Cytology of peritoneal washings
:*Omentectomy
:*Biopsies of peritoneal surfaces

=== Prevention ===
*There are no primary preventive measures available for mixed Mullerian tumor.
*Once diagnosed and successfully treated, patients with mixed Mullerian tumor are followed-up every 6 or 12 months.
*Follow-up testing include pelvic examination, ultrasound, and biomarker monitorization.

==References==
{{Reflist|2}}

[[Category: Oncology]]

Primary effusion lymphoma

2016-04-21T15:56:01Z

Sergekorjian:

__NOTOC__
{{SI}}

{{CMG}} {{AE}} {{AS}}

{{SK}} Body cavity lymphoma; PEL

==Overview==
Primary effusion lymphoma (PEL) is rare subtype of [[diffuse large B-cell lymphoma]] (DLBCL). Primary effusion lymphoma is a very fast-growing (aggressive) lymphoma usually confined to pleural, pericardial, peritoneal body cavities, presenting as serous effusions without detectable tumor masses, occurring primarily but not exclusively in HIV-infected patients. Lymphoma cells are found in the fluid in these body cavities. Primary effusion lymphoma is associated with [[human herpes virus 8]] (HHV8) infection and Epstein-Barr virus ([[EBV]]) infection. On microscopic histopathological analysis, neoplastic proliferation of large lymphoid cells with round to irregular nuclei, prominent nucleoli, and varying amounts of vacuolated cytoplasm are characteristic findings of primary effusion lymphoma. Primary effusion lymphoma is more commonly observed among young or middle aged patients. Males are more commonly affected with primary effusion lymphoma than females. Symptoms of primary effusion lymphoma may include [[fever]], [[fatigue]], [[weight loss]], [[night sweats]], painless swellings in the neck, axilla, groin, thorax, and abdomen, chest pain, abdomen pain, bones pain, and skin rash. A [[lymph node biopsy]] is diagnostic of primary effusion lymphoma. The mainstay of therapy for primary effusion lymphoma is [[chemotherapy]] and [[antiretroviral therapy]].

==Pathophysiology==
* Primary effusion lymphoma is associated with [[human herpes virus 8]] (HHV8) infection and Epstein-Barr virus ([[EBV]]) infection.<ref name= canadiancancer>Primary effusion lymphona. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/primary-effusion-lymphoma/?region=nb. Accessed on March 23, 2016 </ref>
* Primary effusion lymphoma most often occurs in people with weakened immune systems, such as those with [[HIV/AIDS]]. It can sometimes occur in people who have had organ transplants.
* On microscopic histopathological analysis, neoplastic proliferation of large lymphoid cells with round to irregular nuclei, prominent nucleoli, and varying amounts of vacuolated cytoplasm are characteristic findings of primary effusion lymphoma. There were immunoblastic, plasmablastic and anaplastic variants with bizarre, pleomorphic nuclei.<ref name= biomedcentral>Primary effusion lymphona. BioMed Central. http://jmedicalcasereports.biomedcentral.com/articles/10.1186/1752-1947-5-60. Accessed on March 23, 2016 </ref>
<gallery widths=200px>
Image: Microscopic pathology of primary effusion lymphoma.jpg | At light microscopy, the sample consisted of a frankly neoplastic population provided with plasmablastic and/or anaplastic morphology (Figure 1A), which turned out CD3-, CD20- (Figure 1B), CD79a-, CD45+ (Figure 1C), CD38+, CD30+, IRF4+, LANA-1+ (Figure 1D), EBER+ (Figure 1C inset), and Ki-67>90%. Based on these findings, we made a diagnosis of Primary effusion lymphoma.<ref name= biomedcentral>Primary effusion lymphona. BioMed Central. http://jmedicalcasereports.biomedcentral.com/articles/10.1186/1752-1947-5-60. Accessed on March 23, 2016 </ref>
</gallery>

==Causes==
* There are no established causes for primary effusion lymphoma.

==Differentiating primary effusion lymphoma from other Diseases==
* Primary effusion lymphoma must be differentiated from other diseases such as:
:* Plasmablastic lymphoma
:* [[Burkitt lymphoma]]
:* Pyothorax associated lymphoma

==Epidemiology and Demographics==
===Age===
* Primary effusion lymphoma is more commonly observed among young or middle aged patients.<ref name=seer.cancer.gov>Primary effusion lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf57e3e27c3994bd5378/. Accessed on March 23, 2016 </ref>
===Gender===
* Males are more commonly affected with primary effusion lymphoma than females.<ref name=seer.cancer.gov>Primary effusion lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf57e3e27c3994bd5378/. Accessed on March 23, 2016 </ref>

==Risk Factors==
*There are no established risk factors for primary effusion lymphoma.

== Natural History, Complications and Prognosis==
* Primary effusion lymphoma is a very fast-growing (aggressive) lymphoma usually confined to pleural, pericardial, peritoneal body cavities, presenting as serous effusions without detectable tumor masses, occurring primarily but not exclusively in HIV-infected patients.
* Prognosis is generally poor.
== Diagnosis ==
===Staging===
Staging for primary effusion lymphoma is provided in the following table:<ref>{{Cite journal| doi = 10.1200/JCO.2013.54.8800| issn = 1527-7755| volume = 32| issue = 27| pages = 3059–3068| last1 = Cheson| first1 = Bruce D.| last2 = Fisher| first2 = Richard I.| last3 = Barrington| first3 = Sally F.| last4 = Cavalli| first4 = Franco| last5 = Schwartz| first5 = Lawrence H.| last6 = Zucca| first6 = Emanuele| last7 = Lister| first7 = T. Andrew| last8 = Alliance, Australasian Leukaemia and Lymphoma Group| last9 = Eastern Cooperative Oncology Group| last10 = European Mantle Cell Lymphoma Consortium| last11 = Italian Lymphoma Foundation| last12 = European Organisation for Research| last13 = Treatment of Cancer/Dutch Hemato-Oncology Group| last14 = Grupo Español de Médula Ósea| last15 = German High-Grade Lymphoma Study Group| last16 = German Hodgkin's Study Group| last17 = Japanese Lymphorra Study Group| last18 = Lymphoma Study Association| last19 = NCIC Clinical Trials Group| last20 = Nordic Lymphoma Study Group| last21 = Southwest Oncology Group| last22 = United Kingdom National Cancer Research Institute| title = Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification| journal = Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology| date = 2014-09-20| pmid = 25113753}}</ref>

{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
|+ '''Revised staging system for primary nodal lymphomas (Lugano classification)'''
! style="background: #4479BA; color:#FFF;" | Stage
! style="background: #4479BA; color:#FFF;" | Involvement
! style="background: #4479BA; color:#FFF;" | Extranodal (E) status
|-
| style="padding: 5px 5px; background: #DCDCDC;" colspan=3 | '''Limited'''
|-
| style="padding: 5px 5px; background: #F5F5F5;" | Stage I
| style="padding: 5px 5px; background: #F5F5F5;" | One node or a group of adjacent nodes
| style="padding: 5px 5px; background: #F5F5F5;" | Single extranodal lesions without nodal involvement
|-
| style="padding: 5px 5px; background: #F5F5F5;" | Stage II
| style="padding: 5px 5px; background: #F5F5F5;" | Two or more nodal groups on the same side of the diaphragm
| style="padding: 5px 5px; background: #F5F5F5;" | Stage I or II by nodal extent with limited contiguous extranodal involvement
|-
| style="padding: 5px 5px; background: #F5F5F5;" | Stage II bulky
| style="padding: 5px 5px; background: #F5F5F5;" | II as above with "bulky" disease
| style="padding: 5px 5px; background: #F5F5F5;" | Not applicable
|-
| style="padding: 5px 5px; background: #DCDCDC;" colspan=3 | '''Advanced'''
|-
| style="padding: 5px 5px; background: #F5F5F5;" | Stage III
| style="padding: 5px 5px; background: #F5F5F5;" | Nodes on both sides of the diaphragm; nodes above the diaphragm with spleen involvement
| style="padding: 5px 5px; background: #F5F5F5;" | Not applicable
|-
| style="padding: 5px 5px; background: #F5F5F5;" | Stage IV
| style="padding: 5px 5px; background: #F5F5F5;" | Additional noncontiguous extralymphatic involvement
| style="padding: 5px 5px; background: #F5F5F5;" | Not applicable
|}

=== Symptoms ===
*Symptoms of primary effusion lymphoma may include the following:<ref name=seer.cancer.gov>Primary effusion lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf57e3e27c3994bd5378/. Accessed on March 22, 2016 </ref>
:* [[Fever]]
:* [[Fatigue]]
:* [[Weight loss]]
:* [[Night sweats]]
:* Painless swellings in the neck, axilla, groin, thorax, and abdomen
:* Pain in the chest, abdomen, or bones
:* Skin rash

=== Physical Examination ===
*Physical examination of primary effusion lymphoma may be remarkable for:
:* [[Fever]]
:* Skin rash
:* [[Lymphadenopathy|Cervical lymphadenopathy]]
:* Thoracic masses suggestive of [[Lymphadenopathy|central lymphadenopathy]]
:* [[Abdominal mass]]es suggestive of [[Lymphadenopathy|central lymphadenopathy]]
:* [[Lymphadenopathy|Peripheral lymphadenopathy]]

=== Laboratory Findings ===
*There are no specific laboratory findings associated with primary effusion lymphoma.
*A lymph node biopsy is diagnostic of primary effusion lymphoma.
*Other laboratory findings consistent with the diagnosis of primary effusion lymphoma include [[complete blood count]], blood chemistry studies, cytogenetic analysis, [[flow cytometry]], [[immunohistochemistry]], and [[immunophenotyping]].

===Imaging Findings===
*There are no specific imaging study associated with primary effusion lymphoma.
*[[CT]], [[MRI]], and [[PET]] scan may be helpful in the diagnosis of primary effusion lymphoma.

=== Other Diagnostic Studies ===
*Primary effusion lymphoma may also be diagnosed using [[bone marrow aspiraton]] and [[biopsy]].

== Treatment ==
=== Medical Therapy ===
* The mainstay of therapy for primary effusion lymphoma is [[chemotherapy]] and [[antiretroviral therapy]].<ref name= canadiancancer>Primary effusion lymphona. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/primary-effusion-lymphoma/?region=nb. Accessed on March 23, 2016 </ref>
* Drug regimen: CHOP – [[Cyclophosphamide]] {{and}} [[Doxorubicin]] {{and}} [[Vincristine]] {{and}} [[Prednisone]]

==References==
{{Reflist|2}}
[[Category:Hematology]]
[[Category:Types of cancer]]
[[Category:Oncology]]
[[Category:Disease]]

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{{WikiDoc Sources}}

Meigs syndrome

2016-04-21T15:41:47Z

Sergekorjian:

__NOTOC__
{{SI}}

'''For patient information, please click [[Meigs syndrome (patient information)|here]]'''

{{CMG}} {{AE}} {{MV}}

{{SK}} Demons Meigs syndrome; Meigs-Cass syndrome; Meigs-Salmon syndrome

==Overview==

'''Meigs syndrome''' '''(also known as "Meigs-Cass syndrome")''' is defined as the triad of [[ascites]], [[pleural effusion]], and [[Ovarian tumor|benign ovarian tumor]]. Meigs syndrome was first discovered by Otto von Spiegelberg, a German gynecologist, in 1866.<ref name="pmid20896800">{{cite journal |vauthors=Tait L |title=On the occurrence of Pleural Effusion in association with Disease of the Abdomen |journal=Med Chir Trans |volume=75 |issue= |pages=109–18 |year=1892 |pmid=20896800 |pmc=2036288 |doi= |url=}}</ref> There is no classification system established for Meigs syndrome. Other variants of Meigs syndrome include pseudo-meigs syndrome, and atypical Meigs' syndrome. Meigs syndrome may be caused by either [[ovarian fibroma]], [[Brenner tumor]], [[Thecoma|ovarian thecoma]], or [[Granulosa cell tumour|granulosa cell tumor]].<ref name="wiki">Meigs syndrome. Wikipedia. https://en.wikipedia.org/wiki/Meigs'_syndrome Accessed on March 29, 2016</ref><ref name="radio">Meigs syndrome. Radiopedia. http://radiopaedia.org/articles/meigs-syndrome Accessed on March 29, 2016</ref> The pathogenesis of Meigs syndrome is characterized by a transudative process. The prevalence of benign ovarian tumors is approximately 2-10%, and only 1-2% develop Meigs syndrome.<ref name="pmid22369402">{{cite journal |vauthors=Annaiah TK, Reynolds SF, Lopez C |title=Histology and prevalence of ovarian tumours in postmenopausal women: is follow-up required in all cases? |journal=J Obstet Gynaecol |volume=32 |issue=3 |pages=267–70 |year=2012 |pmid=22369402 |doi=10.3109/01443615.2011.626089 |url=}}</ref> Meigs syndrome is more commonly observed among postmenopausal women. The median age at diagnosis is approximately 50 years. The majority of patients with Meigs syndrome are asymptomatic.<ref name="pmid22369402">{{cite journal |vauthors=Annaiah TK, Reynolds SF, Lopez C |title=Histology and prevalence of ovarian tumours in postmenopausal women: is follow-up required in all cases? |journal=J Obstet Gynaecol |volume=32 |issue=3 |pages=267–70 |year=2012 |pmid=22369402 |doi=10.3109/01443615.2011.626089 |url=}}</ref> Early clinical features include [[bloating]], [[fatigue]], and [[shortness of breath]]. Computed tomography is the imaging modality of choice for Meigs syndrome. On conventional radiography, Meigs syndrome is characterized by blunting of the costophrenic angle or fluid within the horizontal or oblique fissures (250-600 ml of fluid is required before the pleural effusion becomes evident). Surgery is the mainstay of therapy for Meigs syndrome.
[[Laparotomy|Exploratory laparotomy]] with [[Cancer staging|surgical staging]] is the most common approach to the treatment of Meigs syndrome. Once diagnosed and successfully treated, patients with Meigs syndrome are followed-up every 6 months. Follow-up testing includes; serum cancer antigen 125, ultrasound, and basic metabolic profile.<ref name="pmid22369402">{{cite journal |vauthors=Annaiah TK, Reynolds SF, Lopez C |title=Histology and prevalence of ovarian tumours in postmenopausal women: is follow-up required in all cases? |journal=J Obstet Gynaecol |volume=32 |issue=3 |pages=267–70 |year=2012 |pmid=22369402 |doi=10.3109/01443615.2011.626089 |url=}}</ref>

==Historical Perspective==
*Meigs syndrome was first discovered by Otto von Spiegelberg, a German gynecologist, in 1866.<ref name="pmid20896800">{{cite journal |vauthors=Tait L |title=On the occurrence of Pleural Effusion in association with Disease of the Abdomen |journal=Med Chir Trans |volume=75 |issue= |pages=109–18 |year=1892 |pmid=20896800 |pmc=2036288 |doi= |url=}}</ref>
*Meigs syndrome is named after Joe Vincent Meigs, an American gynecologist who defined Meigs syndrome as the presence of ascites, hydrothorax, association with benign ovarian tumor.<ref name="pmid10996681">{{cite journal |vauthors=Lurie S |title=Meigs' syndrome: the history of the eponym |journal=Eur. J. Obstet. Gynecol. Reprod. Biol. |volume=92 |issue=2 |pages=199–204 |year=2000 |pmid=10996681 |doi= |url=}}</ref>
*In 1900, the first therapeutical surgical approach was developed by Albert Jean Octave Demons to treat Meigs syndrome.<ref name="pmid13148256">{{cite journal |vauthors=MEIGS JV |title=Fibroma of the ovary with ascites and hydrothorax; Meigs' syndrome |journal=Am. J. Obstet. Gynecol. |volume=67 |issue=5 |pages=962–85 |year=1954 |pmid=13148256 |doi= |url=}}</ref>

==Classification==
*There is no classification system established for Meigs syndrome.<ref name="pmid25662723">{{cite journal |vauthors=Gil A, Roque A, Alemán C |title=[Meigs' syndrome] |language=Spanish; Castilian |journal=Med Clin (Barc) |volume=145 |issue=2 |pages=95 |year=2015 |pmid=25662723 |doi=10.1016/j.medcli.2014.12.007 |url=}}</ref>
*Other variants of Meigs syndrome include pseudo-meigs syndrome, and atypical Meigs' syndrome.

==Pathophysiology==
*The pathogenesis of Meigs syndrome is characterized by a transudative process.<ref name="ppp">Riker D, Goba D. Ovarian mass, pleural effusion, and ascites: revisiting meigs syndrome. J Bronchology Interv Pulmonol. 2013 Jan. 20(1):48-51.</ref>
*The transudative process consists in the formation of peritoneal and pleural effusion to the filtration of interstitial fluid in the peritoneum through the tumor capsule, and the diffusion to the pleural space.<ref name="pmid8351065">{{cite journal |vauthors=Santopaolo O, Rotondo A, Alfè M, Canciello P, Rito Marcone G, Cusati B |title=[Meigs syndrome with bilateral hydrothorax] |language=Italian |journal=Minerva Ginecol |volume=45 |issue=5 |pages=263–6 |year=1993 |pmid=8351065 |doi= |url=}}</ref>
*There are no genes associated with the development of Meigs syndrome.
*On gross pathology, marked ovarian enlargement, watery cut surface, and no necrosis are characteristic findings of Meigs syndrome.<ref name="pathologyoutlines">Ovary - nontumor. Pathology Outlines. http://www.pathologyoutlines.com/topic/ovarymassiveedema.html Accessed on March 29,2016</ref>
*On microscopic histopathological analysis, variable stromal luteinization, marked edema of stroma surrounding follicles, and stroma around vessels are characteristic findings of Meigs syndrome.<ref name="pathologyoutlines">Ovary - nontumor. Pathology Outlines. http://www.pathologyoutlines.com/topic/ovarymassiveedema.html Accessed on March 29,2016</ref>

==Causes==
* Meigs syndrome may be caused by either ovarian fibroma, Brenner tumor, ovarian thecoma, or granulosa cell tumor.<ref name="wiki">Meigs syndrome. Wikipedia. https://en.wikipedia.org/wiki/Meigs'_syndrome Accessed on March 29, 2016</ref><ref name="radio">Meigs syndrome. Radiopedia. http://radiopaedia.org/articles/meigs-syndrome Accessed on March 29, 2016</ref>
* In general, Meigs syndrome may be caused by any benign ovarian tumor.

==Differentiating Meigs syndrome from other Diseases==
*Meigs syndrome must be differentiated from other diseases that cause bloating, fatigue, and shortness of breath such as:<ref name="pmid23328144">{{cite journal |vauthors=Riker D, Goba D |title=Ovarian mass, pleural effusion, and ascites: revisiting Meigs syndrome |journal=J Bronchology Interv Pulmonol |volume=20 |issue=1 |pages=48–51 |year=2013 |pmid=23328144 |doi=10.1097/LBR.0b013e31827ccb35 |url=}}</ref>
:*[[Ovarian cancer]]
:*[[Cirrhosis]]
:*[[Colon cancer]]
:*[[Tuberculosis]]
:*Milroy's disease

==Epidemiology and Demographics==

===Prevalence===
* The prevalence of Meigs syndrome is unknown.<ref name="pmid22369402">{{cite journal |vauthors=Annaiah TK, Reynolds SF, Lopez C |title=Histology and prevalence of ovarian tumours in postmenopausal women: is follow-up required in all cases? |journal=J Obstet Gynaecol |volume=32 |issue=3 |pages=267–70 |year=2012 |pmid=22369402 |doi=10.3109/01443615.2011.626089 |url=}}</ref>
*The prevalence of benign ovarian tumors is approximately 2-10%, and only 1-2% develop Meigs syndrome.<ref name="pmid22369402">{{cite journal |vauthors=Annaiah TK, Reynolds SF, Lopez C |title=Histology and prevalence of ovarian tumours in postmenopausal women: is follow-up required in all cases? |journal=J Obstet Gynaecol |volume=32 |issue=3 |pages=267–70 |year=2012 |pmid=22369402 |doi=10.3109/01443615.2011.626089 |url=}}</ref>

===Age===
*Meigs syndrome is more commonly observed among postmenopausal women.
*The median age at diagnosis is approximately 50 years.

===Gender===
*Meigs syndrome affects exclusively females.

===Race===
*There is no racial predilection for Meigs syndrome.
*Meigs syndrome usually affects females with higher socioeconomic status.<ref name="pmid22369402">{{cite journal |vauthors=Annaiah TK, Reynolds SF, Lopez C |title=Histology and prevalence of ovarian tumours in postmenopausal women: is follow-up required in all cases? |journal=J Obstet Gynaecol |volume=32 |issue=3 |pages=267–70 |year=2012 |pmid=22369402 |doi=10.3109/01443615.2011.626089 |url=}}</ref>

==Risk Factors==
*Common risk factors in the development of Meigs syndrome are enlarged adnexal mass ( > 5cm), co-existing pleural effusion, and family history of any form of cancer.<ref name="pmid15738016">{{cite journal |vauthors=Simpkins F, Zahurak M, Armstrong D, Grumbine F, Bristow R |title=Ovarian malignancy in breast cancer patients with an adnexal mass |journal=Obstet Gynecol |volume=105 |issue=3 |pages=507–13 |year=2005 |pmid=15738016 |doi=10.1097/01.AOG.0000154162.51442.14 |url=}}</ref>

== Natural History, Complications and Prognosis==
*The majority of patients with Meigs syndrome are asymptomatic.<ref name="pmid22369402">{{cite journal |vauthors=Annaiah TK, Reynolds SF, Lopez C |title=Histology and prevalence of ovarian tumours in postmenopausal women: is follow-up required in all cases? |journal=J Obstet Gynaecol |volume=32 |issue=3 |pages=267–70 |year=2012 |pmid=22369402 |doi=10.3109/01443615.2011.626089 |url=}}</ref>
*Early clinical features include bloating, fatigue, and shortness of breath.
*If left untreated, the majority of patients with Meigs syndrome may progress to develop [[respiratory failure]], [[ovarian torsion]], and [[hypoproteinemia]].
*Common complications of Meigs syndrome include portal vein obstruction, [[inferior vena cava obstruction]], and [[thoracic duct]] obstruction.
*Prognosis is generally good, and the 5 survival rate of patients with Meigs syndrome is approximately 100%.<ref name="pmid22369402">{{cite journal |vauthors=Annaiah TK, Reynolds SF, Lopez C |title=Histology and prevalence of ovarian tumours in postmenopausal women: is follow-up required in all cases? |journal=J Obstet Gynaecol |volume=32 |issue=3 |pages=267–70 |year=2012 |pmid=22369402 |doi=10.3109/01443615.2011.626089 |url=}}</ref>

== Diagnosis ==
===Diagnostic Criteria===
*The diagnosis of Meigs syndrome is made when the following 3 diagnostic criteria are met:
:*Ascities
:*Pleural effusion or [[hydrothorax]]
:*Benign ovarian tumor

=== Symptoms ===
*Meigs syndrome is usually [[asymptomatic]].
*Symptoms of Meigs syndrome may include the following:
:*[[Bloating]]
:*[[Fatigue]]
:*[[Weight-loss]]
:*[[Shortness of breath]]
:*[[Cough]]
:*[[Menstrual disorder|Menstrual irregularity]]

=== Physical Examination ===
*Patients with Meigs syndrome are usually well-appearing.
*Physical examination may be remarkable for:
:*Increased abdominal perimeter
:*Decreased/absent breath sounds
:*Reduced [[chest expansion]]
:*Rapid rate of breathing

=== Laboratory Findings ===
*There are no specific laboratory findings associated with Meigs syndrome.
*In some cases, unspecific laboratory findings may include abnormal [[CA-125 test|serum cancer antigen 125]] test and abnormal prothrombin time.

===Imaging Findings===
*Computed tomography is the imaging modality of choice for Meigs syndrome.
*On conventional radiography, Meigs syndrome is characterized by blunting of the costophrenic angle or fluid within the horizontal or oblique fissures (250-600 ml of fluid is required before the pleural effusion becomes evident)
*On computed tomography, findings include: presence of ascites, and characterization of ovarian mass.
*Ultrasound may demonstrate and confirm the presence of ovarian mass and ascities.

===Other Diagnostic Studies ===
*Meigs syndrome may also be diagnosed using thoracentesis or paracentesis.<ref name="laparoscopy">Meigs' Syndrome: a case presentation and revision of the literature. http://www.obgyn.net/laparoscopy-and-hysteroscopy/meigs-syndrome-case-presentation-and-revision-literature#sthash.NQ3ZxKLh.dpuf Accessed on March 29, 2016 </ref>
*Findings on paracentesis include transudative ascitic fluid, and presence of reactive mesothelial cells.
*Findings on thoracentesis include transudative pleural fluid, and negative for malignant cells.

== Treatment ==
=== Medical Therapy ===
*There is no medical treatment for Meigs syndrome.

=== Surgery ===
*Surgery is the mainstay of therapy for Meigs syndrome.
*Exploratory laparotomy with surgical staging is the most common approach to the treatment of Meigs syndrome.
*Meigs syndrome is a benign condition and the ascites and pleural effusion resolves after resection of the primary pelvic tumor.

=== Prevention ===
*There are no primary preventive measures available for Meigs syndrome.<ref name="pmid22369402">{{cite journal |vauthors=Annaiah TK, Reynolds SF, Lopez C |title=Histology and prevalence of ovarian tumours in postmenopausal women: is follow-up required in all cases? |journal=J Obstet Gynaecol |volume=32 |issue=3 |pages=267–70 |year=2012 |pmid=22369402 |doi=10.3109/01443615.2011.626089 |url=}}</ref>
*Once diagnosed and successfully treated, patients with Meigs syndrome are followed-up every 6 months.
*Follow-up testing includes; serum cancer antigen 125, ultrasound, and basic metabolic profile.<ref name="pmid22369402">{{cite journal |vauthors=Annaiah TK, Reynolds SF, Lopez C |title=Histology and prevalence of ovarian tumours in postmenopausal women: is follow-up required in all cases? |journal=J Obstet Gynaecol |volume=32 |issue=3 |pages=267–70 |year=2012 |pmid=22369402 |doi=10.3109/01443615.2011.626089 |url=}}</ref>
==References==
{{Reflist|2}}

Desmoplastic small round cell tumor

2016-04-21T15:01:38Z

Sergekorjian:

__NOTOC__
{{SI}}
{{CMG}}{{AE}}{{SR}}

{{SK}} Desmoplastic small round cell tumour; Desmoplastic small round blue cell tumor; Desmoplastic small round blue cell tumour; Intraabdominal desmoplastic small round blue cell tumor; Desmoplastic small cell tumor; Desmoplastic cancer; Desmoplastic sarcoma; DSRCT; Mesothelioblastoma; Polyphenotypic small round cell tumor

==Overview==
Desmoplastic small round cell tumor is an extremely rare, highly aggressive, and malignant neoplasm initially reported by Gerald and Rosai in 1989. The pathogenesis or histogenesis of desmoplastic small round cell tumor is uncertain; it mainly occurs in adolescents and mostly involves the abdominal and/or pelvic peritoneum. Moreover, it was also reported in [[epididymis]], [[pleura]], soft tissues, [[bone]], [[ovary]], and [[kidney]]. The diagnosis can be confirmed by histological and immunohistochemistry studies. CT scan is the most widely used diagnostic modality; abdominopelvic site was the commonest presentation and the disease can occur at other nonserosal surfaces also. Despite multimodality treatments, optimal treatment strategies remain controversial and the prognosis is poor. Current multimodality treatment rarely achieves cure and prolongs life. Here, we described 12 cases of abdominal DSRCT and retrospectively analyzed its clinical, radiological, and biopathological features, highlighting the modalities of treatment.<ref name="ZhangLiu2014">{{cite journal|last1=Zhang|first1=Guangzhao|last2=Liu|first2=Guangjun|last3=Zhao|first3=Dahua|last4=Cui|first4=Xijun|last5=Li|first5=Gang|title=Desmoplastic Small Round Cell Tumor of the Abdomen and Pelvis: Clinicopathological Characters of 12 Cases|journal=The Scientific World Journal|volume=2014|year=2014|pages=1–7|issn=2356-6140|doi=10.1155/2014/549612}}</ref>

==Historical Perspective==
Desmoplastic small round cell tumor was first described by pathologists, William L. Gerald and Juan Rosai, in 1989.<ref name="ZhangLiu2014">{{cite journal|last1=Zhang|first1=Guangzhao|last2=Liu|first2=Guangjun|last3=Zhao|first3=Dahua|last4=Cui|first4=Xijun|last5=Li|first5=Gang|title=Desmoplastic Small Round Cell Tumor of the Abdomen and Pelvis: Clinicopathological Characters of 12 Cases|journal=The Scientific World Journal|volume=2014|year=2014|pages=1–7|issn=2356-6140|doi=10.1155/2014/549612}}</ref>

==Pathophysiology==
===Pathogenesis===
Desmoplastic small round cell tumor is a highly aggressive, rare tumor of mesenchymal origin whose oncogenic effect is presumed to originate from the unique chromosomal translocation t(11;22)(p13:q12), leading to the fusion of the N-terminal domain of Ewing’s sarcoma gene ''[[Ewing sarcoma breakpoint region 1|EWS]]'', to the C-terminal domain of Wilms’ tumor suppressor gene, ''[[WT1]]'', which is found in most but not all desmoplastic small round cell tumors.<ref name="LettieriGarcia-Filion2014">{{cite journal|last1=Lettieri|first1=Christina K.|last2=Garcia-Filion|first2=Pamela|last3=Hingorani|first3=Pooja|title=Incidence and Outcomes of Desmoplastic Small Round Cell Tumor: Results from the Surveillance, Epidemiology, and End Results Database|journal=Journal of Cancer Epidemiology|volume=2014|year=2014|pages=1–5|issn=1687-8558|doi=10.1155/2014/680126}}</ref>

===Genetics===
Desmoplastic small round cell tumor is associated with a unique chromosomal translocation t(11;22)(p13:q12), resulting in an ''[[Ewing sarcoma breakpoint region 1|EWS]]''/''[[WT1]]'' transcript that is diagnostic of this tumor. This transcript codes for a protein that acts as a transcriptional activator that fails to suppress tumor growth. The ''[[Ewing sarcoma breakpoint region 1|EWS]]''/''[[WT1]]'' translocation product targets [[SLC29A4|ENT4]]. ENT4 is also known as [[SLC29A4|PMAT]].<ref name=causesdsrct1>Causes of desmoplastic small round cell tumor. Wikipedia 2016. https://en.wikipedia.org/wiki/Desmoplastic_small-round-cell_tumor#Differential_Diagnoses. Accessed on March 29, 2016</ref>

===Associated Conditions===
There may be a chimeric relationship between desmoplastic small round cell tumor, and [[Wilms' tumor]] and [[Ewing's sarcoma]]. Together with [[neuroblastoma]] and [[non-Hodgkin's lymphoma]], they form the small cell tumors.<ref name=causesdsrct1>Causes of desmoplastic small round cell tumor. Wikipedia 2016. https://en.wikipedia.org/wiki/Desmoplastic_small-round-cell_tumor#Differential_Diagnoses. Accessed on March 29, 2016</ref>

===Gross Pathology===
*On gross pathology, desmoplastic small giant cell tumor is characterized by a mass demonstrating the presence of nonuniform white-gray multinodules, distributed widely in the peritoneum.<ref name="ZhangLiu2014">{{cite journal|last1=Zhang|first1=Guangzhao|last2=Liu|first2=Guangjun|last3=Zhao|first3=Dahua|last4=Cui|first4=Xijun|last5=Li|first5=Gang|title=Desmoplastic Small Round Cell Tumor of the Abdomen and Pelvis: Clinicopathological Characters of 12 Cases|journal=The Scientific World Journal|volume=2014|year=2014|pages=1–7|issn=2356-6140|doi=10.1155/2014/549612}}</ref>
*Desmoplastic small round cell tumor tends to grow along a serosal lining, most commonly the [[peritoneum|peritoneal surface]], but other primary sites have been described.<ref name="LettieriGarcia-Filion2014">{{cite journal|last1=Lettieri|first1=Christina K.|last2=Garcia-Filion|first2=Pamela|last3=Hingorani|first3=Pooja|title=Incidence and Outcomes of Desmoplastic Small Round Cell Tumor: Results from the Surveillance, Epidemiology, and End Results Database|journal=Journal of Cancer Epidemiology|volume=2014|year=2014|pages=1–5|issn=1687-8558|doi=10.1155/2014/680126}}</ref>

===Microscopic Pathology===
On microscopic histopathological analysis, desmoplastic small round cell tumor is characterized by:<ref name=microdsrct1>icroscopic features of desmoplastic small round cell tumour. Libre pathology 2016. https://librepathology.org/wiki/Desmoplastic_small_round_cell_tumour. Accessed on March 30, 2016</ref><ref name="KisO'Regan2012">{{cite journal|last1=Kis|first1=B|last2=O'Regan|first2=K N|last3=Agoston|first3=A|last4=Javery|first4=O|last5=Jagannathan|first5=J|last6=Ramaiya|first6=N H|title=Imaging of desmoplastic small round cell tumour in adults|journal=The British Journal of Radiology|volume=85|issue=1010|year=2012|pages=187–192|issn=0007-1285|doi=10.1259/bjr/57186741}}</ref>
*Broad bands of paucicellular fibrous stroma
*Small round cells in nests with an undulating sharp border
:*The small round cells lack distinct [[nucleoli]] and have scant [[cytoplasm]]; they are small round cell tumor cells.
*[[mitoses|Abundant mitoses]]
*+/-[[Necrosis]]
*Hyperplastic blood vessels

====Gallery====
<gallery>
Image:Desmoplastic small round cell tumour - intermed mag.jpg|Micrograph of a desmoplastic small round cell tumor, showing the characteristic desmoplastic stroma and angulated nests of small round cells on H&E stain.<ref name=microscopicimagedsrct1>Desmoplastic small round cell tumor. Wikipedia 2016. Accessed on March 29, 2016</ref>
Image:Dsrct1.jpg|Display of small round blue cells characteristic of desmoplastic small-round-cell tumor.<ref name=microscopicimagedsrct1>Desmoplastic small round cell tumor. Wikipedia 2016. Accessed on March 29, 2016</ref>
Image:Dsrct2.jpg|Cell exhibiting blue oval and round shapes of desmoplastic small round blue cell tumor.<ref name=microscopicimagedsrct1>Desmoplastic small round cell tumor. Wikipedia 2016. Accessed on March 29, 2016</ref>

</gallery>

===Immunohistochemistry===
Desmoplastic small round cell tumor is demonstrated by positivity to tumor markers, such as:<ref name=microdsrct1>icroscopic features of desmoplastic small round cell tumour. Libre pathology 2016. https://librepathology.org/wiki/Desmoplastic_small_round_cell_tumour. Accessed on March 30, 2016</ref><ref name="ZhangLiu2014">{{cite journal|last1=Zhang|first1=Guangzhao|last2=Liu|first2=Guangjun|last3=Zhao|first3=Dahua|last4=Cui|first4=Xijun|last5=Li|first5=Gang|title=Desmoplastic Small Round Cell Tumor of the Abdomen and Pelvis: Clinicopathological Characters of 12 Cases|journal=The Scientific World Journal|volume=2014|year=2014|pages=1–7|issn=2356-6140|doi=10.1155/2014/549612}}</ref>
*[[SLC4A3|AE1/AE3]]
*[[Desmin]]
*[[Vimentin]]
*EMA
*[[neuron-specific enolase|Neuron-specific enolase (NSE)]]
*[[WT1|WT1 (C-terminal)]]
*[[CD57]]

==Causes==
Common causes of desmoplastic small round cell tumor include [[mutation|genetic mutations]]. A [[translocation|chromosomal translocation]], t(11;22)(p13:q12) resulting in an ''[[Ewing sarcoma breakpoint region 1|EWS]]''/''[[WT1]]'' transcript, may result in formation of desmoplastic small round cell tumor. This transcript codes for a protein that acts as a transcriptional activator that fails to suppress tumor growth. The ''[[Ewing sarcoma breakpoint region 1|EWS]]''/''[[WT1]]'' translocation product targets [[SLC29A4|ENT4]]. ENT4 is also known as [[SLC29A4|PMAT]].<ref name=causesdsrct1>Causes of desmoplastic small round cell tumor. Wikipedia 2016. https://en.wikipedia.org/wiki/Desmoplastic_small-round-cell_tumor#Differential_Diagnoses. Accessed on March 29, 2016</ref>

==Differentiating Desmoplastic Small Round Cell Tumor from other Diseases==
*Desmoplastic small round cell tumor in the abdomen may cause gastrointestinal symptoms and mimic other abdominal tumors. So, they must be differentiated from other tumors in the abdomen, such as:<ref name=ddxdsrct1>Differential diagnosis of desmoplastic small round cell tumor. Wikipedia 2016. https://en.wikipedia.org/wiki/Desmoplastic_small-round-cell_tumor#Differential_Diagnoses. Accessed on March 29, 2016</ref>
:*[[Rhabdomyosarcoma]]
:*[[Neuroblastoma]]
:*[[carcinoid|Mesenteric carcinoid]]
*In older patients, desmoplastic small round cell tumor must be differentiated from:<ref name=ddxdsrct1>Differential diagnosis of desmoplastic small round cell tumor. Wikipedia 2016. https://en.wikipedia.org/wiki/Desmoplastic_small-round-cell_tumor#Differential_Diagnoses. Accessed on March 29, 2016</ref><ref name=radiopaediaddxdsrct2>Differential diagnosis of desmoplastic small round cell tumour. Dr Yuranga Weerakkody and Dr Ayush Goel et al. Radiopaedia 2016. http://radiopaedia.org/articles/desmoplastic-small-round-cell-tumour. Accessed on March 29, 2016</ref>
:*[[Non-Hodgkins lymphoma]]
:*[[Peritoneal mesothelioma]]
:*[[Peritoneal carcinomatosis]]
*In males, desmoplastic small round cell tumor may be mistaken for [[testicular cancer|testicular germ cell tumor]] while in females, desmoplastic small round cell tumor may be mistaken for [[ovarian cancer]].<ref name=ddxdsrct1>Differential diagnosis of desmoplastic small round cell tumor. Wikipedia 2016. https://en.wikipedia.org/wiki/Desmoplastic_small-round-cell_tumor#Differential_Diagnoses. Accessed on March 29, 2016</ref>
*Desmoplastic small round cell tumor must be differentiated from other small-round blue cell cancers, such as:<ref name=ddxdsrct1>Differential diagnosis of desmoplastic small round cell tumor. Wikipedia 2016. https://en.wikipedia.org/wiki/Desmoplastic_small-round-cell_tumor#Differential_Diagnoses. Accessed on March 29, 2016</ref><ref name=smallroundbluecelltumours1>Small round blue cell tumours. Dr Yuranga Weerakkody and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/small-round-blue-cell-tumours. Accessed on March 29, 2016</ref>
:*[[Ewing sarcoma]]
:*[[Neuroblastoma]]
:*[[rhabdomyosarcoma|Embryonal rhabdomyosarcoma]]
:*[[Pineoblastoma]]
:*[[Wilms tumor]]
:*[[Retinoblastoma]]
:*[[Hepatoblastoma]]
:*[[PNET|CNS primitive neuroectodermal tumor (CNS-PNET)]]
:*[[PNET|Peripheral primitive neuroectodermal tumor (pPNET)]]
:*Askin tumor
:*Neuroepithelioma
:*[[Acute leukemia]]
:*[[mesothelioma|Small cell mesothelioma]]

==Epidemiology and Demographics==
===Incidence===
*Age-adjusted incidence rate of desmoplastic small round cell tumor for African Americans and Caucasians is 0.05 and 0.02 per 100,000 individuals, respectively.<ref name="LettieriGarcia-Filion2014">{{cite journal|last1=Lettieri|first1=Christina K.|last2=Garcia-Filion|first2=Pamela|last3=Hingorani|first3=Pooja|title=Incidence and Outcomes of Desmoplastic Small Round Cell Tumor: Results from the Surveillance, Epidemiology, and End Results Database|journal=Journal of Cancer Epidemiology|volume=2014|year=2014|pages=1–5|issn=1687-8558|doi=10.1155/2014/680126}}</ref>
*The overall age-adjusted incidence rate of desmoplastic small round cell tumor is 0.03 per 100,000 individuals, with a peak incidence of 0.074 per 100,000 individuals in the 20–24 years of age group.<ref name="LettieriGarcia-Filion2014">{{cite journal|last1=Lettieri|first1=Christina K.|last2=Garcia-Filion|first2=Pamela|last3=Hingorani|first3=Pooja|title=Incidence and Outcomes of Desmoplastic Small Round Cell Tumor: Results from the Surveillance, Epidemiology, and End Results Database|journal=Journal of Cancer Epidemiology|volume=2014|year=2014|pages=1–5|issn=1687-8558|doi=10.1155/2014/680126}}</ref>

===Age===
*Desmoplastic small round cell tumor is a rare disease that tends to affect children and young adults.
*Peak age of incidence for desmoplastic small round cell tumor is between 20 and 24 years.<ref name="LettieriGarcia-Filion2014">{{cite journal|last1=Lettieri|first1=Christina K.|last2=Garcia-Filion|first2=Pamela|last3=Hingorani|first3=Pooja|title=Incidence and Outcomes of Desmoplastic Small Round Cell Tumor: Results from the Surveillance, Epidemiology, and End Results Database|journal=Journal of Cancer Epidemiology|volume=2014|year=2014|pages=1–5|issn=1687-8558|doi=10.1155/2014/680126}}</ref>

===Gender===
Males are more commonly affected with desmoplastic small round cell tumor than females. The male to female ratio is approximately 4 to 1.<ref name="LettieriGarcia-Filion2014">{{cite journal|last1=Lettieri|first1=Christina K.|last2=Garcia-Filion|first2=Pamela|last3=Hingorani|first3=Pooja|title=Incidence and Outcomes of Desmoplastic Small Round Cell Tumor: Results from the Surveillance, Epidemiology, and End Results Database|journal=Journal of Cancer Epidemiology|volume=2014|year=2014|pages=1–5|issn=1687-8558|doi=10.1155/2014/680126}}</ref>

===Race===
Desmoplatic small round cell tumor usually affects individuals of the African American and Caucasian race. Latin American and Asian individuals are less likely to develop desmoplatic small round cell tumor.<ref name="LettieriGarcia-Filion2014">{{cite journal|last1=Lettieri|first1=Christina K.|last2=Garcia-Filion|first2=Pamela|last3=Hingorani|first3=Pooja|title=Incidence and Outcomes of Desmoplastic Small Round Cell Tumor: Results from the Surveillance, Epidemiology, and End Results Database|journal=Journal of Cancer Epidemiology|volume=2014|year=2014|pages=1–5|issn=1687-8558|doi=10.1155/2014/680126}}</ref>
====Gallery====
[[Image:Gender and race DSRCT.PNG|500px]] (a) Overall age-adjusted incidence of desmoplastic small round cell tumor, (b) Sex-based age-adjusted incidence of desmoplastic small round cell tumor. Males are more likely than females to get desmoplastic small round cell tumor, (c) Race-based, age-adjusted incidence of DSRCT. African Americans are more likely than Caucasians to get desmoplastic small round cell tumor.<ref name="LettieriGarcia-Filion2014">{{cite journal|last1=Lettieri|first1=Christina K.|last2=Garcia-Filion|first2=Pamela|last3=Hingorani|first3=Pooja|title=Incidence and Outcomes of Desmoplastic Small Round Cell Tumor: Results from the Surveillance, Epidemiology, and End Results Database|journal=Journal of Cancer Epidemiology|volume=2014|year=2014|pages=1–5|issn=1687-8558|doi=10.1155/2014/680126}}</ref>

===Demographics===
[[Image:DSRCT.jpg|600px]] From Christina K. Lettieri et al.<ref name="LettieriGarcia-Filion2014">{{cite journal|last1=Lettieri|first1=Christina K.|last2=Garcia-Filion|first2=Pamela|last3=Hingorani|first3=Pooja|title=Incidence and Outcomes of Desmoplastic Small Round Cell Tumor: Results from the Surveillance, Epidemiology, and End Results Database|journal=Journal of Cancer Epidemiology|volume=2014|year=2014|pages=1–5|issn=1687-8558|doi=10.1155/2014/680126}}</ref>

==Risk Factors==
There are no established risk factors for desmoplastic small round cell tumor.<ref name=riskfactorsdesmoplaticsmallroundcelltumor1>Causes of desmoplastic small round cell tumor. Wikipedia 2016. https://en.wikipedia.org/wiki/Desmoplastic_small-round-cell_tumor. Accessed on March 29, 2016</ref>

==Natural History, Complications, and Prognosis==
===Natural History===
Because the disease can be misdiagnosed or remain undetected, tumors frequently grow large within the abdomen and metastasize or seed to other parts of the body.<ref name="Hayes-JordanAnderson2011">{{cite journal|last1=Hayes-Jordan|first1=Andrea|last2=Anderson|first2=Peter M|title=The diagnosis and management of desmoplastic small round cell tumor: a review|journal=Current Opinion in Oncology|volume=23|issue=4|year=2011|pages=385–389|issn=1040-8746|doi=10.1097/CCO.0b013e3283477aab}}</ref>

===Complications===
Complication sof desmoplastic small round cell tumor include:<ref name="NabiSaste2015">{{cite journal|last1=Nabi|first1=Shahzaib|last2=Saste|first2=Abhijit|last3=Gulati|first3=Rohit|title=A Rare Case of Metastatic Desmoplastic Small Round Cell Tumour: Diagnosis and Management|journal=Case Reports in Oncological Medicine|volume=2015|year=2015|pages=1–6|issn=2090-6706|doi=10.1155/2015/925453}}</ref><ref name=radiographicftrsdsrct1>Radiographic features of desmoplastic small round cell tumour. Dr Yuranga Weerakkody and Dr Ayush Goel et al. Radioipaedia 2016. http://radiopaedia.org/articles/desmoplastic-small-round-cell-tumour. Accessed on March 29, 2016</ref>
*[[peritoneum|Peritoneal seeding]]
*[[Lymph node|Lymph nodal involvement]]
*[[Metastasis]] ([[liver mass|liver]], [[bone mass|bone]], [[lung mass|lung]])

===Prognosis===
*The prognosis for desmoplastic small round cell tumor remains poor and depends upon the stage of the cancer.
*The 5-year overall survival rate of patients with desmoplastic small round cell tumor is approximately 15%.<ref name="Hayes-JordanAnderson2011">{{cite journal|last1=Hayes-Jordan|first1=Andrea|last2=Anderson|first2=Peter M|title=The diagnosis and management of desmoplastic small round cell tumor: a review|journal=Current Opinion in Oncology|volume=23|issue=4|year=2011|pages=385–389|issn=1040-8746|doi=10.1097/CCO.0b013e3283477aab}}</ref>

====Gallery====
[[Image:Prognosis DSRCT.PNG|600px]] (a) Race-based survival of desmoplastic small round cell tumor. There may be a survival disadvantage for African americans compared to Caucasians. Although it did not reach statistical significance, this analysis suggests that African americans are 33% more likely to succumb to desmoplastic small round cell tumor than are Caucasians, (b) Treatment-based survival of desmoplastic small round cell tumor, radiation versus no radiation. There was no statistically significant difference in survival amongst patients who received radiation therapy compared to those who did not, (c) Treatment-based survival of demsoplastic small round cell tumor, radiation after surgery versus no radiation. Patients who received radiation following surgery fared better than those patients who did not. 
From Christina K. Lettieri et al.<ref name="LettieriGarcia-Filion2014">{{cite journal|last1=Lettieri|first1=Christina K.|last2=Garcia-Filion|first2=Pamela|last3=Hingorani|first3=Pooja|title=Incidence and Outcomes of Desmoplastic Small Round Cell Tumor: Results from the Surveillance, Epidemiology, and End Results Database|journal=Journal of Cancer Epidemiology|volume=2014|year=2014|pages=1–5|issn=1687-8558|doi=10.1155/2014/680126}}</ref>

==Diagnosis==
===Symptoms===
*There are few early warning signs that a patient has a desmoplastic small round cell tumor.
*Patients are often young and healthy as the tumors grow and spread uninhibited within the abdominal cavity. These are rare tumors and the symptoms are often misdiagnosed by physicians. The abdominal lump may grow to enormous size before being noticed by the patient.<ref name=smdsrct1>Symptoms of desmoplastic small round cell tumor. Wikipedia 2016. https://en.wikipedia.org/wiki/Desmoplastic_small-round-cell_tumor#Differential_Diagnoses. Accessed on March 29, 2016</ref>

====Common Symptoms====
Common symptoms of desmoplastic small round cell tumor include:<ref name=smdsrct1>Symptoms of desmoplastic small round cell tumor. Wikipedia 2016. https://en.wikipedia.org/wiki/Desmoplastic_small-round-cell_tumor#Differential_Diagnoses. Accessed on March 29, 2016</ref><ref name="ZhangLiu2014">{{cite journal|last1=Zhang|first1=Guangzhao|last2=Liu|first2=Guangjun|last3=Zhao|first3=Dahua|last4=Cui|first4=Xijun|last5=Li|first5=Gang|title=Desmoplastic Small Round Cell Tumor of the Abdomen and Pelvis: Clinicopathological Characters of 12 Cases|journal=The Scientific World Journal|volume=2014|year=2014|pages=1–7|issn=2356-6140|doi=10.1155/2014/549612}}</ref>
*[[Abdominal distention]]
*[[Abdominal mass|Lump in abdomen]]
*[[Abdominal pain]]
*[[Vomiting]]
*[[Back pain]]
*[[intestinal obstruction|Gastrointestinal obstruction]]
*[[anorexia|Lack of appetite]]
*[[Fatigue]]
*[[Weakness]]
*[[Cachexia]]

====Less Common Symptoms====
Less common symptoms of desmoplastic small round cell tumor include:<ref name=smdsrct1>Symptoms of desmoplastic small round cell tumor. Wikipedia 2016. https://en.wikipedia.org/wiki/Desmoplastic_small-round-cell_tumor#Differential_Diagnoses. Accessed on March 29, 2016</ref>
*[[lump|Unknown lumps]]
*[[thyroid gland|Thyroid conditions]]
*[[endocrinology|Hormonal problems]]
*[[Blood clotting|Blood clotting problems]]
*[[renal disease|Kidney or urological problems]]
*Lump in the [[testicle]], [[breast]], [[uterus]], [[Vestibule of the vagina|vagina]], or [[ovary]]

===Physical Examination===
Common physical examination findings of desmoplastic small round cell tumor include:<ref name="KisO'Regan2012">{{cite journal|last1=Kis|first1=B|last2=O'Regan|first2=K N|last3=Agoston|first3=A|last4=Javery|first4=O|last5=Jagannathan|first5=J|last6=Ramaiya|first6=N H|title=Imaging of desmoplastic small round cell tumour in adults|journal=The British Journal of Radiology|volume=85|issue=1010|year=2012|pages=187–192|issn=0007-1285|doi=10.1259/bjr/57186741}}</ref><ref name="ZhangLiu2014">{{cite journal|last1=Zhang|first1=Guangzhao|last2=Liu|first2=Guangjun|last3=Zhao|first3=Dahua|last4=Cui|first4=Xijun|last5=Li|first5=Gang|title=Desmoplastic Small Round Cell Tumor of the Abdomen and Pelvis: Clinicopathological Characters of 12 Cases|journal=The Scientific World Journal|volume=2014|year=2014|pages=1–7|issn=2356-6140|doi=10.1155/2014/549612}}</ref>
*[[abdominal mass|Palpable adominal mass]]
*[[Ascites]]
*Increased abdominal girth

===CT===
*Abdominal CT scan is the most widely used diagnostic modality for desmoplastic small round cell tumor.<ref name="ZhangLiu2014">{{cite journal|last1=Zhang|first1=Guangzhao|last2=Liu|first2=Guangjun|last3=Zhao|first3=Dahua|last4=Cui|first4=Xijun|last5=Li|first5=Gang|title=Desmoplastic Small Round Cell Tumor of the Abdomen and Pelvis: Clinicopathological Characters of 12 Cases|journal=The Scientific World Journal|volume=2014|year=2014|pages=1–7|issn=2356-6140|doi=10.1155/2014/549612}}</ref>
*Findings on CT scan suggestive of desmoplastic small round cell tumor include a solitary to multiple soft tissue masses with no definite organ of origin, usually in the retrovesical or rectouterine space, which enhance heterogenously on contrast studies. [[Necrosis]], [[hemorrhage]], and [[fibrosis|fibrous components]] are common.
*[[peritoneum|Peritoneal seeding]], [[lymph node|lymph nodal involvement]], [[metastasis|liver and bone metastases]] may also be demonstrated.<ref name=radiographicftrsdsrct1>Radiographic features of desmoplastic small round cell tumour. Dr Yuranga Weerakkody and Dr Ayush Goel et al. Radioipaedia 2016. http://radiopaedia.org/articles/desmoplastic-small-round-cell-tumour. Accessed on March 29, 2016</ref>

====Gallery====
<gallery>
Image:Ct image dsrct.jpg|Abdominopelvic CT scan revealed diffuse multiple soft-tissue masses in peritoneal and mesenteric surfaces.<ref name="ZhangLiu2014">{{cite journal|last1=Zhang|first1=Guangzhao|last2=Liu|first2=Guangjun|last3=Zhao|first3=Dahua|last4=Cui|first4=Xijun|last5=Li|first5=Gang|title=Desmoplastic Small Round Cell Tumor of the Abdomen and Pelvis: Clinicopathological Characters of 12 Cases|journal=The Scientific World Journal|volume=2014|year=2014|pages=1–7|issn=2356-6140|doi=10.1155/2014/549612}}</ref>
Image:Ct image 2 dsrct.jpg|Contrast-enhanced CT revealed the heterogeneous mass with obvious enhancement areas and scattered low attenuation.<ref name="ZhangLiu2014">{{cite journal|last1=Zhang|first1=Guangzhao|last2=Liu|first2=Guangjun|last3=Zhao|first3=Dahua|last4=Cui|first4=Xijun|last5=Li|first5=Gang|title=Desmoplastic Small Round Cell Tumor of the Abdomen and Pelvis: Clinicopathological Characters of 12 Cases|journal=The Scientific World Journal|volume=2014|year=2014|pages=1–7|issn=2356-6140|doi=10.1155/2014/549612}}</ref>

</gallery>

===MRI===
*MRI may helpful in delineating the extent of desmoplastic small round cell tumor, if surgery is considered.<ref name="KisO'Regan2012">{{cite journal|last1=Kis|first1=B|last2=O'Regan|first2=K N|last3=Agoston|first3=A|last4=Javery|first4=O|last5=Jagannathan|first5=J|last6=Ramaiya|first6=N H|title=Imaging of desmoplastic small round cell tumour in adults|journal=The British Journal of Radiology|volume=85|issue=1010|year=2012|pages=187–192|issn=0007-1285|doi=10.1259/bjr/57186741}}</ref>
*On MRI, desmoplastic small round cell tumor is characterized by hypo- to isointensity on T1-weighted images. On contrast administration, it has a heterogenous enhancement, due to the fibrous stroma and degenerative features including [[necrosis]], [[hemorrhage]], and [[calcification].<ref name="KisO'Regan2012">{{cite journal|last1=Kis|first1=B|last2=O'Regan|first2=K N|last3=Agoston|first3=A|last4=Javery|first4=O|last5=Jagannathan|first5=J|last6=Ramaiya|first6=N H|title=Imaging of desmoplastic small round cell tumour in adults|journal=The British Journal of Radiology|volume=85|issue=1010|year=2012|pages=187–192|issn=0007-1285|doi=10.1259/bjr/57186741}}</ref>

==Treatment==
*Desmoplastic small round cell tumor is frequently misdiagnosed. Adult patients should always be referred to a sarcoma specialist. This is an aggressive, rare, fast spreading tumor and both pediatric and adult patients should be treated at a sarcoma center.<ref name=rxofdsrct1>Treatment of desmoplastic small round cell tumor. Wikipedia 2016. https://en.wikipedia.org/wiki/Desmoplastic_small-round-cell_tumor. Accessed on March 30, 2016</ref>
*[[surgery|Surgical excision]] with [[combination chemotherapy]] as an adjunct is mandatory for nonmetastatic cases because these modalities used in isolation may have less impact.<ref name="ZhangLiu2014">{{cite journal|last1=Zhang|first1=Guangzhao|last2=Liu|first2=Guangjun|last3=Zhao|first3=Dahua|last4=Cui|first4=Xijun|last5=Li|first5=Gang|title=Desmoplastic Small Round Cell Tumor of the Abdomen and Pelvis: Clinicopathological Characters of 12 Cases|journal=The Scientific World Journal|volume=2014|year=2014|pages=1–7|issn=2356-6140|doi=10.1155/2014/549612}}</ref>
*There is no standard protocol for desmoplastic small round cell tumor; however, recent journals and studies have reported that some patients respond to high-dose (P6 Protocol) [[chemotherapy]], maintenance chemotherapy, [[debulking procedure]], [[cytoreductive surgery]], and [[radiotherapy|radiation therapy]].
*Other treatment options for desmoplastic small round cell tumor include [[stem cell transplant|hematopoietic stem cell transplantation]], intensity-modulated radiation Therapy, [[radiofrequency ablation]], stereotactic body radiation therapy, intraperitoneal hyperthermic chemoperfusion, and clinical trials.

==References==
{{reflist|2}}

[[Category:Types of cancer]]
[[Category:Oncology]]
[[Category:Disease]]

{{WS}}
{{WH}}

Angiosarcoma

2016-04-21T14:32:10Z

Sergekorjian:

__NOTOC__
{{SI}}
{{CMG}}
==Overview==
==References==
{{reflist|2}}

[[Category:Oncology]]

Angiosarcoma

2016-04-21T14:31:22Z

Sergekorjian:

__NOTOC__
{{SI}}
{{CMG}}
==Overview==
==References==
{{reflist|2}}

Hemangiosarcoma

2016-04-21T14:30:20Z

Sergekorjian: ←Redirected page to Angiosarcoma

#redirect[[Angiosarcoma]]

Encephalitis

2016-04-21T14:16:11Z

Sergekorjian:

__NOTOC__
{{CMG}}

Common encephalidites include:

===[[Viral encephalitis]]===
*[[Herpes simplex encephalitis]]
*[[VZV encephalitis]]

===[[Vector-borne encephalitis]]===
*[[Tick-borne encephalitis]]
*[[California encephalitis virus|California encephalitis]]
*[[Eastern equine encephalitis]]
*[[Western equine encephalitis]]
*[[Japanese Encephalitis|Japanese encephalitis]]
*[[Venezuelan equine encephalitis]]
*[[West Nile encephalitis]]
*[[La Crosse encephalitis]]
*[[St. Louis encephalitis]]

===[[Fungal encephalitis]]===

===[[Protozoan encephalitis]]===
*[[Granulomatous amebic encephalitis]]
*[[Toxoplasmic encephalitis]]

==Comprehensive List of Causes of Encephalitis & Encephalopathy==
{|style="width:75%; height:100px" border="1"
|-bgcolor="LightSteelBlue"
| '''Infectious Disease'''
|bgcolor="Beige"| [[alkhurma virus]], [[Borrelia burgdorferi]], [[botulism]], [[brome mosaic virus]], [[California encephalitis virus]], [[campylobacter fetus]], [[capnocytophaga canimorsus]], [[cardiovirus]], [[cat scratch disease]], [[cercopithecine herpesvirus 1]], [[Chagas disease]], [[chandipura virus]], [[chicken pox]], [[coccidioides spp]], [[Colorado tick fever]], [[congenital herpes simplex]], [[congenital rubella syndrome]], [[congenital syphilis]], [[coxiella burnetii ]], [[coxsackievirus]], [[Creutzfeldt-Jakob disease]], [[cryptococcosis]], [[cryptococcus neoformans]], [[cysticercosis]], [[cytomegalovirus]], [[dengue fever]], [[diphtheria]], [[duvenhage virus]], [[Eastern equine encephalitis virus]], [[Ebstein-Barr virus]], [[ehrlichia|ehrlichia chaffeensis]], [[ehrlichiosis]], [[elizabethkingia meningoseptica]], [[enterobacter sakazakii]], [[enterovirus 70]], [[enterovirus|enterovirus 71]], [[enteroviruses]], [[escherichia coli]], [[feline viral rhinotracheitis]], [[human parainfluenza viruses classification|fetal parainfluenza virus type 3]], [[flavivirus|flavivirus infections]], [[flu]], [[gnathostomiasis|gnathostoma hispidum infection]], [[gnathostoma spinigerum]], [[gnathostoma spinigerum|gnathostoma spinigerum infection]], [[gnathostomiasis]], [[group B streptococcal infection|streptococcus, group B]], [[haemophilus influenzae]], [[hand-foot-and-mouth disease]], [[hantavirosis ]], [[hemorrhagic fever]], [[hendra virus]], [[henipavirus]], [[hepatitis E virus]], [[herpes B virus]], [[herpes simplex virus]], [[histoplasma capsulatum]], [[HIV]], [[ehrlichiosis|human granulocytotrophic ehrlichiosis]], [[human herpesvirus 6]], [[ehrlichiosis|human monocytotrophic ehrlichiosis]], [[subacute sclerosing panencephalitis|immunosuppressive measles encephalitis]], [[infectious canine hepatitis]], [[influenza virus]], [[Japanese encephalitis]], [[JC virus]], [[klebsiella]], [[tick-borne encephalitis|kumlinge virus encephalitis]], [[kunjin virus]], [[La Crosse encephalitis]], [[labyrinthitis]], [[lassa fever]], [[listeria monocytogenes]], [[listeriosis ]], [[louping ill]], [[Lyme disease]], [[lymphocytic choriomeningitis]], [[lyssavirus]], [[malaria]], [[measles]], [[mokola virus]], [[mononucleosis ]], [[mumps ]], [[mumps virus]], [[Murray Valley encephalitis virus]], [[mycobacterium avium-intracellulare]], [[mycobacterium tuberculosis]], [[mycoplasma pneumoniae]], [[naegleria fowleri]], [[neisseria meningiditis]], [[neonatal herpes]], [[nipah virus]], [[nocardia]], [[pertussis]], [[phlebovirus]], [[pneumococcus]], [[poliomyelitis]], [[pontiac fever]], [[Powassan virus]], [[poxviridae disease]], [[primary amoebic meningoencephalitis ]], [[encephalitis classification|primary encephalitis]], [[progressive multifocal leukoencephalopathy]], [[pseudomonas aeruginosa]], [[psittacosis]], [[Q fever]], [[rickettsia|Queensland tick typhus]], [[rabies]], [[Rasmussen's encephalitis]], [[rickettsiae]], [[Rift Valley fever]], [[tropical disease|rocio encephalitis]], [[Rocky Mountain spotted fever]], [[rubella]], [[salmonella typhi]], [[schistosoma japonicum]], [[encephalitis classification|secondary encephalitis]], [[shingles]], [[polyomavirus|Simian B virus infection]], [[sinusitis]], [[St. Louis encephalitis]], [[staphylococcus aureus]], [[streptococcus pneumoniae]], [[streptococcus suis]], [[subacute sclerosing panencephalitis]], [[taenia solium]], [[tick-borne encephalitis]], [[togaviridae disease]], [[TORCH syndrome]], [[toxocariasis]], [[toxoplasma gondii]], [[toxoplasmosis]], [[trench fever]], [[treponema pallidum]], [[trichinella]], [[trichinosis]], [[tropheryma whipplei]], [[trypanosoma brucei gambiense]], [[trypanosomiasis]], [[typhoid fever]], [[vaccinia]], [[varicella zoster]], [[varicella zoster virus]], [[Venezuelan equine encephalitis]], [[viral encephalitis]], [[visna virus]], [[West Nile fever]], [[Western equine encephalitis]], [[Western equine encephalitis virus]], [[whooping cough]], [[yersinia pestis]]
|-
|}

{|style="width:75%; height:100px" border="1"
|style="height:100px"; style="width:25%" border="1" bgcolor="LightSteelBlue" | '''Cardiovascular'''
|style="height:100px"; style="width:75%" border="1" bgcolor="Beige" |[[Kawasaki disease]]
|-
|-bgcolor="LightSteelBlue"
| '''Chemical / poisoning'''
|bgcolor="Beige"| [[Arsenic]], [[heavy metal ingestion|heavy metal toxicity]], [[icaridin]], [[organophosphate poisoning]], [[poison hemlock]], [[thallium]]
|-
|-bgcolor="LightSteelBlue"
| '''Dermatologic'''
|bgcolor="Beige"| [[Behcet disease]], [[systemic lupus erythematosus]], [[Vogt-Koyanagi-Harada syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Drug Side Effect'''
|bgcolor="Beige"| [[Acyclovir]], [[interferon]], [[kynurenic acid]], [[levodopa]], [[methamphetamine]], [[trimethobenzamide]], [[zanamivir]]
|-
|-bgcolor="LightSteelBlue"
| '''Ear Nose Throat'''
|bgcolor="Beige"| [[Cholesteatoma]], [[labyrinthitis]], [[sinusitis]]
|-
|-bgcolor="LightSteelBlue"
| '''Endocrine'''
|bgcolor="Beige"|[[Myasthenia gravis]]
|-
|-bgcolor="LightSteelBlue"
| '''Environmental'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Gastroenterologic'''
|bgcolor="Beige"| [[Porphyria]], [[Reye's syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Genetic'''
|bgcolor="Beige"| [[Aicardi-Goutières syndrome]], [[biotinidase deficiency]], [[familial histiocytic reticulosis]], [[hemophagocytic reticulosis]], [[ornithine transcarbamylase deficiency]], [[porphyria]], [[Smith-Magenis syndrome|Smith disease]], [[Tourette syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Hematologic'''
|bgcolor="Beige"| [[Familial histiocytic reticulosis]], [[hemophagocytic reticulosis]], [[autoimmune lymphoproliferative syndrome|lymphoproliferative syndrome]], [[porphyria]], [[x-linked agammaglobulinemia]]
|-
|-bgcolor="LightSteelBlue"
| '''Iatrogenic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Musculoskeletal / Ortho'''
|bgcolor="Beige"| [[myopathy|Metabolic myopathies]], [[multiple sclerosis]], [[skull fracture]]
|-
|-bgcolor="LightSteelBlue"
| '''Neurologic'''
|bgcolor="Beige"| [[Aicardi-Goutières syndrome]], [[amyotrophic lateral sclerosis]], [[aseptic meningitis]], [[cauda equina syndrome]], [[cerebral palsy]], [[chronic inflammatory demyelinating polyneuropathy]], [[conus medullaris]], [[Creutzfeldt-Jakob disease]], [[Lennox-Gastaut syndrome]], [[multiple sclerosis]], [[opsoclonus myoclonus syndrome]], [[paraneoplastic syndrome|paraneoplastic neurologic disorders]], [[poliomyelitis]], [[progressive multifocal leukoencephalopathy]], [[Rasmussen syndrome]], [[Schilder's disease]], [[St. Louis encephalitis]], [[status epilepticus]], [[subacute sclerosing panencephalitis]], [[temporal lobe epilepsy]], [[Tourette syndrome]], [[tourettism]], [[Vogt-Koyanagi-Harada syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Nutritional / Metabolic'''
|bgcolor="Beige"| [[Biotinidase deficiency]], [[myopathy|metabolic myopathies]], [[ornithine transcarbamylase deficiency]]
|-
|-bgcolor="LightSteelBlue"
| '''Obstetric/Gynecologic'''
|bgcolor="Beige"|[[TORCH syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Oncologic'''
|bgcolor="Beige"|[[paraneoplastic syndrome|Paraneoplastic neurologic disorders]]
|-
|-bgcolor="LightSteelBlue"
| '''Opthalmologic'''
|bgcolor="Beige"|[[Vogt-Koyanagi-Harada syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Overdose / Toxicity'''
|bgcolor="Beige"| [[Heavy metal ingestion|Heavy metal toxicity]], [[Reye's syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Psychiatric'''
|bgcolor="Beige"|[[Progressive multifocal leukoencephalopathy]], [[shaken baby syndrome]], [[Tourette syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Pulmonary'''
|bgcolor="Beige"| [[Flu]], [[pertussis]], [[whooping cough]]
|-
|-bgcolor="LightSteelBlue"
| '''Renal / Electrolyte'''
|bgcolor="Beige"|[[Systemic lupus erythematosus]]
|-
|-bgcolor="LightSteelBlue"
| '''Rheum / Immune / Allergy'''
|bgcolor="Beige"| [[Behcet disease]], [[chronic inflammatory demyelinating polyneuropathy]], [[multiple sclerosis]], [[systemic lupus erythematosus]], [[x-linked agammaglobulinemia]]
|-
|-bgcolor="LightSteelBlue"
| '''Sexual'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Trauma'''
|bgcolor="Beige"| [[Cauda equina syndrome]], [[shaken baby syndrome]], [[skull fracture]]
|-
|-bgcolor="LightSteelBlue"
| '''Urologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Miscellaneous'''
|bgcolor="Beige"| [[Porphyria]]
|-
|}

[[Category:Infectious disease]]

Encephalitis

2016-04-21T14:15:42Z

Sergekorjian: /* Encephalitis */

__NOTOC__
{{CMG}}
Common encephalidites include:

===[[Viral encephalitis]]===
*[[Herpes simplex encephalitis]]
*[[VZV encephalitis]]

===[[Vector-borne encephalitis]]===
*[[Tick-borne encephalitis]]
*[[California encephalitis virus|California encephalitis]]
*[[Eastern equine encephalitis]]
*[[Western equine encephalitis]]
*[[Japanese Encephalitis|Japanese encephalitis]]
*[[Venezuelan equine encephalitis]]
*[[West Nile encephalitis]]
*[[La Crosse encephalitis]]
*[[St. Louis encephalitis]]

===[[Fungal encephalitis]]===

===[[Protozoan encephalitis]]===
*[[Granulomatous amebic encephalitis]]
*[[Toxoplasmic encephalitis]]

==Comprehensive List of Causes of Encephalitis & Encephalopathy==
{|style="width:75%; height:100px" border="1"
|-bgcolor="LightSteelBlue"
| '''Infectious Disease'''
|bgcolor="Beige"| [[alkhurma virus]], [[Borrelia burgdorferi]], [[botulism]], [[brome mosaic virus]], [[California encephalitis virus]], [[campylobacter fetus]], [[capnocytophaga canimorsus]], [[cardiovirus]], [[cat scratch disease]], [[cercopithecine herpesvirus 1]], [[Chagas disease]], [[chandipura virus]], [[chicken pox]], [[coccidioides spp]], [[Colorado tick fever]], [[congenital herpes simplex]], [[congenital rubella syndrome]], [[congenital syphilis]], [[coxiella burnetii ]], [[coxsackievirus]], [[Creutzfeldt-Jakob disease]], [[cryptococcosis]], [[cryptococcus neoformans]], [[cysticercosis]], [[cytomegalovirus]], [[dengue fever]], [[diphtheria]], [[duvenhage virus]], [[Eastern equine encephalitis virus]], [[Ebstein-Barr virus]], [[ehrlichia|ehrlichia chaffeensis]], [[ehrlichiosis]], [[elizabethkingia meningoseptica]], [[enterobacter sakazakii]], [[enterovirus 70]], [[enterovirus|enterovirus 71]], [[enteroviruses]], [[escherichia coli]], [[feline viral rhinotracheitis]], [[human parainfluenza viruses classification|fetal parainfluenza virus type 3]], [[flavivirus|flavivirus infections]], [[flu]], [[gnathostomiasis|gnathostoma hispidum infection]], [[gnathostoma spinigerum]], [[gnathostoma spinigerum|gnathostoma spinigerum infection]], [[gnathostomiasis]], [[group B streptococcal infection|streptococcus, group B]], [[haemophilus influenzae]], [[hand-foot-and-mouth disease]], [[hantavirosis ]], [[hemorrhagic fever]], [[hendra virus]], [[henipavirus]], [[hepatitis E virus]], [[herpes B virus]], [[herpes simplex virus]], [[histoplasma capsulatum]], [[HIV]], [[ehrlichiosis|human granulocytotrophic ehrlichiosis]], [[human herpesvirus 6]], [[ehrlichiosis|human monocytotrophic ehrlichiosis]], [[subacute sclerosing panencephalitis|immunosuppressive measles encephalitis]], [[infectious canine hepatitis]], [[influenza virus]], [[Japanese encephalitis]], [[JC virus]], [[klebsiella]], [[tick-borne encephalitis|kumlinge virus encephalitis]], [[kunjin virus]], [[La Crosse encephalitis]], [[labyrinthitis]], [[lassa fever]], [[listeria monocytogenes]], [[listeriosis ]], [[louping ill]], [[Lyme disease]], [[lymphocytic choriomeningitis]], [[lyssavirus]], [[malaria]], [[measles]], [[mokola virus]], [[mononucleosis ]], [[mumps ]], [[mumps virus]], [[Murray Valley encephalitis virus]], [[mycobacterium avium-intracellulare]], [[mycobacterium tuberculosis]], [[mycoplasma pneumoniae]], [[naegleria fowleri]], [[neisseria meningiditis]], [[neonatal herpes]], [[nipah virus]], [[nocardia]], [[pertussis]], [[phlebovirus]], [[pneumococcus]], [[poliomyelitis]], [[pontiac fever]], [[Powassan virus]], [[poxviridae disease]], [[primary amoebic meningoencephalitis ]], [[encephalitis classification|primary encephalitis]], [[progressive multifocal leukoencephalopathy]], [[pseudomonas aeruginosa]], [[psittacosis]], [[Q fever]], [[rickettsia|Queensland tick typhus]], [[rabies]], [[Rasmussen's encephalitis]], [[rickettsiae]], [[Rift Valley fever]], [[tropical disease|rocio encephalitis]], [[Rocky Mountain spotted fever]], [[rubella]], [[salmonella typhi]], [[schistosoma japonicum]], [[encephalitis classification|secondary encephalitis]], [[shingles]], [[polyomavirus|Simian B virus infection]], [[sinusitis]], [[St. Louis encephalitis]], [[staphylococcus aureus]], [[streptococcus pneumoniae]], [[streptococcus suis]], [[subacute sclerosing panencephalitis]], [[taenia solium]], [[tick-borne encephalitis]], [[togaviridae disease]], [[TORCH syndrome]], [[toxocariasis]], [[toxoplasma gondii]], [[toxoplasmosis]], [[trench fever]], [[treponema pallidum]], [[trichinella]], [[trichinosis]], [[tropheryma whipplei]], [[trypanosoma brucei gambiense]], [[trypanosomiasis]], [[typhoid fever]], [[vaccinia]], [[varicella zoster]], [[varicella zoster virus]], [[Venezuelan equine encephalitis]], [[viral encephalitis]], [[visna virus]], [[West Nile fever]], [[Western equine encephalitis]], [[Western equine encephalitis virus]], [[whooping cough]], [[yersinia pestis]]
|-
|}

==Non-Infectious Encephalitis==
{|style="width:75%; height:100px" border="1"
|style="height:100px"; style="width:25%" border="1" bgcolor="LightSteelBlue" | '''Cardiovascular'''
|style="height:100px"; style="width:75%" border="1" bgcolor="Beige" |[[Kawasaki disease]]
|-
|-bgcolor="LightSteelBlue"
| '''Chemical / poisoning'''
|bgcolor="Beige"| [[Arsenic]], [[heavy metal ingestion|heavy metal toxicity]], [[icaridin]], [[organophosphate poisoning]], [[poison hemlock]], [[thallium]]
|-
|-bgcolor="LightSteelBlue"
| '''Dermatologic'''
|bgcolor="Beige"| [[Behcet disease]], [[systemic lupus erythematosus]], [[Vogt-Koyanagi-Harada syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Drug Side Effect'''
|bgcolor="Beige"| [[Acyclovir]], [[interferon]], [[kynurenic acid]], [[levodopa]], [[methamphetamine]], [[trimethobenzamide]], [[zanamivir]]
|-
|-bgcolor="LightSteelBlue"
| '''Ear Nose Throat'''
|bgcolor="Beige"| [[Cholesteatoma]], [[labyrinthitis]], [[sinusitis]]
|-
|-bgcolor="LightSteelBlue"
| '''Endocrine'''
|bgcolor="Beige"|[[Myasthenia gravis]]
|-
|-bgcolor="LightSteelBlue"
| '''Environmental'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Gastroenterologic'''
|bgcolor="Beige"| [[Porphyria]], [[Reye's syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Genetic'''
|bgcolor="Beige"| [[Aicardi-Goutières syndrome]], [[biotinidase deficiency]], [[familial histiocytic reticulosis]], [[hemophagocytic reticulosis]], [[ornithine transcarbamylase deficiency]], [[porphyria]], [[Smith-Magenis syndrome|Smith disease]], [[Tourette syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Hematologic'''
|bgcolor="Beige"| [[Familial histiocytic reticulosis]], [[hemophagocytic reticulosis]], [[autoimmune lymphoproliferative syndrome|lymphoproliferative syndrome]], [[porphyria]], [[x-linked agammaglobulinemia]]
|-
|-bgcolor="LightSteelBlue"
| '''Iatrogenic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Musculoskeletal / Ortho'''
|bgcolor="Beige"| [[myopathy|Metabolic myopathies]], [[multiple sclerosis]], [[skull fracture]]
|-
|-bgcolor="LightSteelBlue"
| '''Neurologic'''
|bgcolor="Beige"| [[Aicardi-Goutières syndrome]], [[amyotrophic lateral sclerosis]], [[aseptic meningitis]], [[cauda equina syndrome]], [[cerebral palsy]], [[chronic inflammatory demyelinating polyneuropathy]], [[conus medullaris]], [[Creutzfeldt-Jakob disease]], [[Lennox-Gastaut syndrome]], [[multiple sclerosis]], [[opsoclonus myoclonus syndrome]], [[paraneoplastic syndrome|paraneoplastic neurologic disorders]], [[poliomyelitis]], [[progressive multifocal leukoencephalopathy]], [[Rasmussen syndrome]], [[Schilder's disease]], [[St. Louis encephalitis]], [[status epilepticus]], [[subacute sclerosing panencephalitis]], [[temporal lobe epilepsy]], [[Tourette syndrome]], [[tourettism]], [[Vogt-Koyanagi-Harada syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Nutritional / Metabolic'''
|bgcolor="Beige"| [[Biotinidase deficiency]], [[myopathy|metabolic myopathies]], [[ornithine transcarbamylase deficiency]]
|-
|-bgcolor="LightSteelBlue"
| '''Obstetric/Gynecologic'''
|bgcolor="Beige"|[[TORCH syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Oncologic'''
|bgcolor="Beige"|[[paraneoplastic syndrome|Paraneoplastic neurologic disorders]]
|-
|-bgcolor="LightSteelBlue"
| '''Opthalmologic'''
|bgcolor="Beige"|[[Vogt-Koyanagi-Harada syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Overdose / Toxicity'''
|bgcolor="Beige"| [[Heavy metal ingestion|Heavy metal toxicity]], [[Reye's syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Psychiatric'''
|bgcolor="Beige"|[[Progressive multifocal leukoencephalopathy]], [[shaken baby syndrome]], [[Tourette syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Pulmonary'''
|bgcolor="Beige"| [[Flu]], [[pertussis]], [[whooping cough]]
|-
|-bgcolor="LightSteelBlue"
| '''Renal / Electrolyte'''
|bgcolor="Beige"|[[Systemic lupus erythematosus]]
|-
|-bgcolor="LightSteelBlue"
| '''Rheum / Immune / Allergy'''
|bgcolor="Beige"| [[Behcet disease]], [[chronic inflammatory demyelinating polyneuropathy]], [[multiple sclerosis]], [[systemic lupus erythematosus]], [[x-linked agammaglobulinemia]]
|-
|-bgcolor="LightSteelBlue"
| '''Sexual'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Trauma'''
|bgcolor="Beige"| [[Cauda equina syndrome]], [[shaken baby syndrome]], [[skull fracture]]
|-
|-bgcolor="LightSteelBlue"
| '''Urologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Miscellaneous'''
|bgcolor="Beige"| [[Porphyria]]
|-
|}

[[Category:Infectious disease]]

Encephalitis

2016-04-21T14:14:13Z

Sergekorjian: /* Overview */

__NOTOC__
{{CMG}}
==Encephalitis==
Common causes of encephalitis include:
===[[Viral encephalitis]]===
*[[Herpes simplex encephalitis]]
*[[VZV encephalitis]]

===[[Vector-borne encephalitis]]===
*[[Tick-borne encephalitis]]
*[[California encephalitis virus|California encephalitis]]
*[[Eastern equine encephalitis]]
*[[Western equine encephalitis]]
*[[Japanese Encephalitis|Japanese encephalitis]]
*[[Venezuelan equine encephalitis]]
*[[West Nile encephalitis]]
*[[La Crosse encephalitis]]
*[[St. Louis encephalitis]]

===[[Fungal encephalitis]]===

===[[Protozoan encephalitis]]===
*[[Granulomatous amebic encephalitis]]
*[[Toxoplasmic encephalitis]]

A comprehensive list of infectious agents that may cause encephalitis is shown below:
{|style="width:75%; height:100px" border="1"
|-bgcolor="LightSteelBlue"
| '''Infectious Disease'''
|bgcolor="Beige"| [[alkhurma virus]], [[Borrelia burgdorferi]], [[botulism]], [[brome mosaic virus]], [[California encephalitis virus]], [[campylobacter fetus]], [[capnocytophaga canimorsus]], [[cardiovirus]], [[cat scratch disease]], [[cercopithecine herpesvirus 1]], [[Chagas disease]], [[chandipura virus]], [[chicken pox]], [[coccidioides spp]], [[Colorado tick fever]], [[congenital herpes simplex]], [[congenital rubella syndrome]], [[congenital syphilis]], [[coxiella burnetii ]], [[coxsackievirus]], [[Creutzfeldt-Jakob disease]], [[cryptococcosis]], [[cryptococcus neoformans]], [[cysticercosis]], [[cytomegalovirus]], [[dengue fever]], [[diphtheria]], [[duvenhage virus]], [[Eastern equine encephalitis virus]], [[Ebstein-Barr virus]], [[ehrlichia|ehrlichia chaffeensis]], [[ehrlichiosis]], [[elizabethkingia meningoseptica]], [[enterobacter sakazakii]], [[enterovirus 70]], [[enterovirus|enterovirus 71]], [[enteroviruses]], [[escherichia coli]], [[feline viral rhinotracheitis]], [[human parainfluenza viruses classification|fetal parainfluenza virus type 3]], [[flavivirus|flavivirus infections]], [[flu]], [[gnathostomiasis|gnathostoma hispidum infection]], [[gnathostoma spinigerum]], [[gnathostoma spinigerum|gnathostoma spinigerum infection]], [[gnathostomiasis]], [[group B streptococcal infection|streptococcus, group B]], [[haemophilus influenzae]], [[hand-foot-and-mouth disease]], [[hantavirosis ]], [[hemorrhagic fever]], [[hendra virus]], [[henipavirus]], [[hepatitis E virus]], [[herpes B virus]], [[herpes simplex virus]], [[histoplasma capsulatum]], [[HIV]], [[ehrlichiosis|human granulocytotrophic ehrlichiosis]], [[human herpesvirus 6]], [[ehrlichiosis|human monocytotrophic ehrlichiosis]], [[subacute sclerosing panencephalitis|immunosuppressive measles encephalitis]], [[infectious canine hepatitis]], [[influenza virus]], [[Japanese encephalitis]], [[JC virus]], [[klebsiella]], [[tick-borne encephalitis|kumlinge virus encephalitis]], [[kunjin virus]], [[La Crosse encephalitis]], [[labyrinthitis]], [[lassa fever]], [[listeria monocytogenes]], [[listeriosis ]], [[louping ill]], [[Lyme disease]], [[lymphocytic choriomeningitis]], [[lyssavirus]], [[malaria]], [[measles]], [[mokola virus]], [[mononucleosis ]], [[mumps ]], [[mumps virus]], [[Murray Valley encephalitis virus]], [[mycobacterium avium-intracellulare]], [[mycobacterium tuberculosis]], [[mycoplasma pneumoniae]], [[naegleria fowleri]], [[neisseria meningiditis]], [[neonatal herpes]], [[nipah virus]], [[nocardia]], [[pertussis]], [[phlebovirus]], [[pneumococcus]], [[poliomyelitis]], [[pontiac fever]], [[Powassan virus]], [[poxviridae disease]], [[primary amoebic meningoencephalitis ]], [[encephalitis classification|primary encephalitis]], [[progressive multifocal leukoencephalopathy]], [[pseudomonas aeruginosa]], [[psittacosis]], [[Q fever]], [[rickettsia|Queensland tick typhus]], [[rabies]], [[Rasmussen's encephalitis]], [[rickettsiae]], [[Rift Valley fever]], [[tropical disease|rocio encephalitis]], [[Rocky Mountain spotted fever]], [[rubella]], [[salmonella typhi]], [[schistosoma japonicum]], [[encephalitis classification|secondary encephalitis]], [[shingles]], [[polyomavirus|Simian B virus infection]], [[sinusitis]], [[St. Louis encephalitis]], [[staphylococcus aureus]], [[streptococcus pneumoniae]], [[streptococcus suis]], [[subacute sclerosing panencephalitis]], [[taenia solium]], [[tick-borne encephalitis]], [[togaviridae disease]], [[TORCH syndrome]], [[toxocariasis]], [[toxoplasma gondii]], [[toxoplasmosis]], [[trench fever]], [[treponema pallidum]], [[trichinella]], [[trichinosis]], [[tropheryma whipplei]], [[trypanosoma brucei gambiense]], [[trypanosomiasis]], [[typhoid fever]], [[vaccinia]], [[varicella zoster]], [[varicella zoster virus]], [[Venezuelan equine encephalitis]], [[viral encephalitis]], [[visna virus]], [[West Nile fever]], [[Western equine encephalitis]], [[Western equine encephalitis virus]], [[whooping cough]], [[yersinia pestis]]
|-
|}

==Non-Infectious Encephalitis==
{|style="width:75%; height:100px" border="1"
|style="height:100px"; style="width:25%" border="1" bgcolor="LightSteelBlue" | '''Cardiovascular'''
|style="height:100px"; style="width:75%" border="1" bgcolor="Beige" |[[Kawasaki disease]]
|-
|-bgcolor="LightSteelBlue"
| '''Chemical / poisoning'''
|bgcolor="Beige"| [[Arsenic]], [[heavy metal ingestion|heavy metal toxicity]], [[icaridin]], [[organophosphate poisoning]], [[poison hemlock]], [[thallium]]
|-
|-bgcolor="LightSteelBlue"
| '''Dermatologic'''
|bgcolor="Beige"| [[Behcet disease]], [[systemic lupus erythematosus]], [[Vogt-Koyanagi-Harada syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Drug Side Effect'''
|bgcolor="Beige"| [[Acyclovir]], [[interferon]], [[kynurenic acid]], [[levodopa]], [[methamphetamine]], [[trimethobenzamide]], [[zanamivir]]
|-
|-bgcolor="LightSteelBlue"
| '''Ear Nose Throat'''
|bgcolor="Beige"| [[Cholesteatoma]], [[labyrinthitis]], [[sinusitis]]
|-
|-bgcolor="LightSteelBlue"
| '''Endocrine'''
|bgcolor="Beige"|[[Myasthenia gravis]]
|-
|-bgcolor="LightSteelBlue"
| '''Environmental'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Gastroenterologic'''
|bgcolor="Beige"| [[Porphyria]], [[Reye's syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Genetic'''
|bgcolor="Beige"| [[Aicardi-Goutières syndrome]], [[biotinidase deficiency]], [[familial histiocytic reticulosis]], [[hemophagocytic reticulosis]], [[ornithine transcarbamylase deficiency]], [[porphyria]], [[Smith-Magenis syndrome|Smith disease]], [[Tourette syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Hematologic'''
|bgcolor="Beige"| [[Familial histiocytic reticulosis]], [[hemophagocytic reticulosis]], [[autoimmune lymphoproliferative syndrome|lymphoproliferative syndrome]], [[porphyria]], [[x-linked agammaglobulinemia]]
|-
|-bgcolor="LightSteelBlue"
| '''Iatrogenic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Musculoskeletal / Ortho'''
|bgcolor="Beige"| [[myopathy|Metabolic myopathies]], [[multiple sclerosis]], [[skull fracture]]
|-
|-bgcolor="LightSteelBlue"
| '''Neurologic'''
|bgcolor="Beige"| [[Aicardi-Goutières syndrome]], [[amyotrophic lateral sclerosis]], [[aseptic meningitis]], [[cauda equina syndrome]], [[cerebral palsy]], [[chronic inflammatory demyelinating polyneuropathy]], [[conus medullaris]], [[Creutzfeldt-Jakob disease]], [[Lennox-Gastaut syndrome]], [[multiple sclerosis]], [[opsoclonus myoclonus syndrome]], [[paraneoplastic syndrome|paraneoplastic neurologic disorders]], [[poliomyelitis]], [[progressive multifocal leukoencephalopathy]], [[Rasmussen syndrome]], [[Schilder's disease]], [[St. Louis encephalitis]], [[status epilepticus]], [[subacute sclerosing panencephalitis]], [[temporal lobe epilepsy]], [[Tourette syndrome]], [[tourettism]], [[Vogt-Koyanagi-Harada syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Nutritional / Metabolic'''
|bgcolor="Beige"| [[Biotinidase deficiency]], [[myopathy|metabolic myopathies]], [[ornithine transcarbamylase deficiency]]
|-
|-bgcolor="LightSteelBlue"
| '''Obstetric/Gynecologic'''
|bgcolor="Beige"|[[TORCH syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Oncologic'''
|bgcolor="Beige"|[[paraneoplastic syndrome|Paraneoplastic neurologic disorders]]
|-
|-bgcolor="LightSteelBlue"
| '''Opthalmologic'''
|bgcolor="Beige"|[[Vogt-Koyanagi-Harada syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Overdose / Toxicity'''
|bgcolor="Beige"| [[Heavy metal ingestion|Heavy metal toxicity]], [[Reye's syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Psychiatric'''
|bgcolor="Beige"|[[Progressive multifocal leukoencephalopathy]], [[shaken baby syndrome]], [[Tourette syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Pulmonary'''
|bgcolor="Beige"| [[Flu]], [[pertussis]], [[whooping cough]]
|-
|-bgcolor="LightSteelBlue"
| '''Renal / Electrolyte'''
|bgcolor="Beige"|[[Systemic lupus erythematosus]]
|-
|-bgcolor="LightSteelBlue"
| '''Rheum / Immune / Allergy'''
|bgcolor="Beige"| [[Behcet disease]], [[chronic inflammatory demyelinating polyneuropathy]], [[multiple sclerosis]], [[systemic lupus erythematosus]], [[x-linked agammaglobulinemia]]
|-
|-bgcolor="LightSteelBlue"
| '''Sexual'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Trauma'''
|bgcolor="Beige"| [[Cauda equina syndrome]], [[shaken baby syndrome]], [[skull fracture]]
|-
|-bgcolor="LightSteelBlue"
| '''Urologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Miscellaneous'''
|bgcolor="Beige"| [[Porphyria]]
|-
|}

[[Category:Infectious disease]]

Encephalitis

2016-04-21T14:13:48Z

Sergekorjian: /* Infectious Encephalitis */

__NOTOC__
{{CMG}}
==Overview==
Encephalitis may be either infectious or non-infectious.
==Encephalitis==
Common causes of encephalitis include:
===[[Viral encephalitis]]===
*[[Herpes simplex encephalitis]]
*[[VZV encephalitis]]

===[[Vector-borne encephalitis]]===
*[[Tick-borne encephalitis]]
*[[California encephalitis virus|California encephalitis]]
*[[Eastern equine encephalitis]]
*[[Western equine encephalitis]]
*[[Japanese Encephalitis|Japanese encephalitis]]
*[[Venezuelan equine encephalitis]]
*[[West Nile encephalitis]]
*[[La Crosse encephalitis]]
*[[St. Louis encephalitis]]

===[[Fungal encephalitis]]===

===[[Protozoan encephalitis]]===
*[[Granulomatous amebic encephalitis]]
*[[Toxoplasmic encephalitis]]

A comprehensive list of infectious agents that may cause encephalitis is shown below:
{|style="width:75%; height:100px" border="1"
|-bgcolor="LightSteelBlue"
| '''Infectious Disease'''
|bgcolor="Beige"| [[alkhurma virus]], [[Borrelia burgdorferi]], [[botulism]], [[brome mosaic virus]], [[California encephalitis virus]], [[campylobacter fetus]], [[capnocytophaga canimorsus]], [[cardiovirus]], [[cat scratch disease]], [[cercopithecine herpesvirus 1]], [[Chagas disease]], [[chandipura virus]], [[chicken pox]], [[coccidioides spp]], [[Colorado tick fever]], [[congenital herpes simplex]], [[congenital rubella syndrome]], [[congenital syphilis]], [[coxiella burnetii ]], [[coxsackievirus]], [[Creutzfeldt-Jakob disease]], [[cryptococcosis]], [[cryptococcus neoformans]], [[cysticercosis]], [[cytomegalovirus]], [[dengue fever]], [[diphtheria]], [[duvenhage virus]], [[Eastern equine encephalitis virus]], [[Ebstein-Barr virus]], [[ehrlichia|ehrlichia chaffeensis]], [[ehrlichiosis]], [[elizabethkingia meningoseptica]], [[enterobacter sakazakii]], [[enterovirus 70]], [[enterovirus|enterovirus 71]], [[enteroviruses]], [[escherichia coli]], [[feline viral rhinotracheitis]], [[human parainfluenza viruses classification|fetal parainfluenza virus type 3]], [[flavivirus|flavivirus infections]], [[flu]], [[gnathostomiasis|gnathostoma hispidum infection]], [[gnathostoma spinigerum]], [[gnathostoma spinigerum|gnathostoma spinigerum infection]], [[gnathostomiasis]], [[group B streptococcal infection|streptococcus, group B]], [[haemophilus influenzae]], [[hand-foot-and-mouth disease]], [[hantavirosis ]], [[hemorrhagic fever]], [[hendra virus]], [[henipavirus]], [[hepatitis E virus]], [[herpes B virus]], [[herpes simplex virus]], [[histoplasma capsulatum]], [[HIV]], [[ehrlichiosis|human granulocytotrophic ehrlichiosis]], [[human herpesvirus 6]], [[ehrlichiosis|human monocytotrophic ehrlichiosis]], [[subacute sclerosing panencephalitis|immunosuppressive measles encephalitis]], [[infectious canine hepatitis]], [[influenza virus]], [[Japanese encephalitis]], [[JC virus]], [[klebsiella]], [[tick-borne encephalitis|kumlinge virus encephalitis]], [[kunjin virus]], [[La Crosse encephalitis]], [[labyrinthitis]], [[lassa fever]], [[listeria monocytogenes]], [[listeriosis ]], [[louping ill]], [[Lyme disease]], [[lymphocytic choriomeningitis]], [[lyssavirus]], [[malaria]], [[measles]], [[mokola virus]], [[mononucleosis ]], [[mumps ]], [[mumps virus]], [[Murray Valley encephalitis virus]], [[mycobacterium avium-intracellulare]], [[mycobacterium tuberculosis]], [[mycoplasma pneumoniae]], [[naegleria fowleri]], [[neisseria meningiditis]], [[neonatal herpes]], [[nipah virus]], [[nocardia]], [[pertussis]], [[phlebovirus]], [[pneumococcus]], [[poliomyelitis]], [[pontiac fever]], [[Powassan virus]], [[poxviridae disease]], [[primary amoebic meningoencephalitis ]], [[encephalitis classification|primary encephalitis]], [[progressive multifocal leukoencephalopathy]], [[pseudomonas aeruginosa]], [[psittacosis]], [[Q fever]], [[rickettsia|Queensland tick typhus]], [[rabies]], [[Rasmussen's encephalitis]], [[rickettsiae]], [[Rift Valley fever]], [[tropical disease|rocio encephalitis]], [[Rocky Mountain spotted fever]], [[rubella]], [[salmonella typhi]], [[schistosoma japonicum]], [[encephalitis classification|secondary encephalitis]], [[shingles]], [[polyomavirus|Simian B virus infection]], [[sinusitis]], [[St. Louis encephalitis]], [[staphylococcus aureus]], [[streptococcus pneumoniae]], [[streptococcus suis]], [[subacute sclerosing panencephalitis]], [[taenia solium]], [[tick-borne encephalitis]], [[togaviridae disease]], [[TORCH syndrome]], [[toxocariasis]], [[toxoplasma gondii]], [[toxoplasmosis]], [[trench fever]], [[treponema pallidum]], [[trichinella]], [[trichinosis]], [[tropheryma whipplei]], [[trypanosoma brucei gambiense]], [[trypanosomiasis]], [[typhoid fever]], [[vaccinia]], [[varicella zoster]], [[varicella zoster virus]], [[Venezuelan equine encephalitis]], [[viral encephalitis]], [[visna virus]], [[West Nile fever]], [[Western equine encephalitis]], [[Western equine encephalitis virus]], [[whooping cough]], [[yersinia pestis]]
|-
|}

==Non-Infectious Encephalitis==
{|style="width:75%; height:100px" border="1"
|style="height:100px"; style="width:25%" border="1" bgcolor="LightSteelBlue" | '''Cardiovascular'''
|style="height:100px"; style="width:75%" border="1" bgcolor="Beige" |[[Kawasaki disease]]
|-
|-bgcolor="LightSteelBlue"
| '''Chemical / poisoning'''
|bgcolor="Beige"| [[Arsenic]], [[heavy metal ingestion|heavy metal toxicity]], [[icaridin]], [[organophosphate poisoning]], [[poison hemlock]], [[thallium]]
|-
|-bgcolor="LightSteelBlue"
| '''Dermatologic'''
|bgcolor="Beige"| [[Behcet disease]], [[systemic lupus erythematosus]], [[Vogt-Koyanagi-Harada syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Drug Side Effect'''
|bgcolor="Beige"| [[Acyclovir]], [[interferon]], [[kynurenic acid]], [[levodopa]], [[methamphetamine]], [[trimethobenzamide]], [[zanamivir]]
|-
|-bgcolor="LightSteelBlue"
| '''Ear Nose Throat'''
|bgcolor="Beige"| [[Cholesteatoma]], [[labyrinthitis]], [[sinusitis]]
|-
|-bgcolor="LightSteelBlue"
| '''Endocrine'''
|bgcolor="Beige"|[[Myasthenia gravis]]
|-
|-bgcolor="LightSteelBlue"
| '''Environmental'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Gastroenterologic'''
|bgcolor="Beige"| [[Porphyria]], [[Reye's syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Genetic'''
|bgcolor="Beige"| [[Aicardi-Goutières syndrome]], [[biotinidase deficiency]], [[familial histiocytic reticulosis]], [[hemophagocytic reticulosis]], [[ornithine transcarbamylase deficiency]], [[porphyria]], [[Smith-Magenis syndrome|Smith disease]], [[Tourette syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Hematologic'''
|bgcolor="Beige"| [[Familial histiocytic reticulosis]], [[hemophagocytic reticulosis]], [[autoimmune lymphoproliferative syndrome|lymphoproliferative syndrome]], [[porphyria]], [[x-linked agammaglobulinemia]]
|-
|-bgcolor="LightSteelBlue"
| '''Iatrogenic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Musculoskeletal / Ortho'''
|bgcolor="Beige"| [[myopathy|Metabolic myopathies]], [[multiple sclerosis]], [[skull fracture]]
|-
|-bgcolor="LightSteelBlue"
| '''Neurologic'''
|bgcolor="Beige"| [[Aicardi-Goutières syndrome]], [[amyotrophic lateral sclerosis]], [[aseptic meningitis]], [[cauda equina syndrome]], [[cerebral palsy]], [[chronic inflammatory demyelinating polyneuropathy]], [[conus medullaris]], [[Creutzfeldt-Jakob disease]], [[Lennox-Gastaut syndrome]], [[multiple sclerosis]], [[opsoclonus myoclonus syndrome]], [[paraneoplastic syndrome|paraneoplastic neurologic disorders]], [[poliomyelitis]], [[progressive multifocal leukoencephalopathy]], [[Rasmussen syndrome]], [[Schilder's disease]], [[St. Louis encephalitis]], [[status epilepticus]], [[subacute sclerosing panencephalitis]], [[temporal lobe epilepsy]], [[Tourette syndrome]], [[tourettism]], [[Vogt-Koyanagi-Harada syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Nutritional / Metabolic'''
|bgcolor="Beige"| [[Biotinidase deficiency]], [[myopathy|metabolic myopathies]], [[ornithine transcarbamylase deficiency]]
|-
|-bgcolor="LightSteelBlue"
| '''Obstetric/Gynecologic'''
|bgcolor="Beige"|[[TORCH syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Oncologic'''
|bgcolor="Beige"|[[paraneoplastic syndrome|Paraneoplastic neurologic disorders]]
|-
|-bgcolor="LightSteelBlue"
| '''Opthalmologic'''
|bgcolor="Beige"|[[Vogt-Koyanagi-Harada syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Overdose / Toxicity'''
|bgcolor="Beige"| [[Heavy metal ingestion|Heavy metal toxicity]], [[Reye's syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Psychiatric'''
|bgcolor="Beige"|[[Progressive multifocal leukoencephalopathy]], [[shaken baby syndrome]], [[Tourette syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Pulmonary'''
|bgcolor="Beige"| [[Flu]], [[pertussis]], [[whooping cough]]
|-
|-bgcolor="LightSteelBlue"
| '''Renal / Electrolyte'''
|bgcolor="Beige"|[[Systemic lupus erythematosus]]
|-
|-bgcolor="LightSteelBlue"
| '''Rheum / Immune / Allergy'''
|bgcolor="Beige"| [[Behcet disease]], [[chronic inflammatory demyelinating polyneuropathy]], [[multiple sclerosis]], [[systemic lupus erythematosus]], [[x-linked agammaglobulinemia]]
|-
|-bgcolor="LightSteelBlue"
| '''Sexual'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Trauma'''
|bgcolor="Beige"| [[Cauda equina syndrome]], [[shaken baby syndrome]], [[skull fracture]]
|-
|-bgcolor="LightSteelBlue"
| '''Urologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Miscellaneous'''
|bgcolor="Beige"| [[Porphyria]]
|-
|}

[[Category:Infectious disease]]

Eastern equine encephalitis virus

2016-04-21T13:54:12Z

Sergekorjian:

__NOTOC__
{{SI}}
{{CMG}}
==Overview==
'''Eastern equine encephalomyelitis virus (EEE)''', commonly called sleeping sickness or "Triple E", is a [[zoonosis|zoonotic]] [[alphavirus]] and [[arbovirus]] present in North, Central and South America and the Caribbean. EEEV was first recognised in [[Massachusetts]], [[USA]] in 1831 when 75 [[horse]]s died of [[encephalitis|encephalitic]] illness. Epizootics in horses have continued to occur regularly in USA. EEE is found today in the eastern part of the country and is often associated with coastal plains.

The causal agent, EEE, was first isolated from infected horse brains in 1933. In 1938, the first confirmed human cases were identified when thirty children died of encephalitis in northeastern USA. These cases coincided with outbreaks in horses in the same regions. The fatality rate in humans is 35% and there is currently no cure for human infections.

EEE is capable of infecting a wide range of animals including mammals, birds, reptiles and amphibians. The virus is maintained in nature through a bird - mosquito cycle. There are two mosquito species primarily involved in this portion of the cycle, they are ''Culiseta melanura'' and ''Cs. morsitans''. These mosquitoes feed on the blood of birds. The amount of virus found in nature increases throughout the summer as more birds and more mosquitoes become infected. Transmission of EEEV to mammals occurs via other mosquitoes. These other mosquitoes are called bridge vectors because they bring the virus from avian populations to mammalian populations. They include '' Coquiletidia perturbans, Aedes vexans, Ochlerotatus sollicitans '' and ''Oc. canadensis''. All these mosquitoes are primarily mammalian feeders. Generally, people only become sick through the bite of an infected mosquito. Humans, horses and other infected mammals do not circulate enough virus in their blood to infect additional mosquitoes. There have been some cases where EEEV has been contracted through lab exposures or from exposure of the eyes, lungs or skin wounds to brain or spinal cord matter from infected animals.

Symptoms in horses occur 1-3 weeks after infection and began with a fever that may reach as high as 106 degrees fahrenheit (41 degrees celsius). The fever usually lasts for 24-48 hours. Nervous signs appear during the fever that include sensitivity to sound, period of excitement, and restlessness. Brain lesions appear causing drowsiness, drooping ears, circling, and abnormal gait. Paralysis follows causing the horse to have difficulty raising its head. The horses usually suffers complete paralysis and death 2-4 days after symptoms appear. Mortality rates among horses with the eastern strain range from 70 to 90%.

[[Image:Eastern equine encephalitis incidence map.gif|left|300px|Disease incidence map for human cases of EEE, 1964-2004]]
The disease can be prevented in horses with the use of [[vaccination]]s. These vaccinations are usually given together with vaccinations for other diseases, most commonly [[Western equine encephalitis virus|WEE]], [[Venezuelan equine encephalitis virus|VEE]], and [[tetanus]]. Most vaccinations for EEE consist of the killed virus.

Several states in the northeast US have seen increased virus activity since 2004. Between 2004 and 2006 there were at least 10 human cases of EEE reported in Massachusetts. In 2006, approximately 500,000 acres in southeastern Massachusetts were treated with mosquito adulticides to reduce the risk of humans contracting EEE. There have been several human cases reported in New Hampshire as well. [http://www.boston.com/news/local/massachusetts/articles/2006/08/18/mosquito_borne_virus_infects_2d_in_mass/][http://www.boston.com/news/globe/city_region/breaking_news/2006/08/middleborough_b.html]

In October of 2007 a citizen of [[Livingston, West Lothian]], [[Scotland]] became the first European victim of this disease. The man had visited New Hampshire during the summer of 2007 on a fishing vacation and was diagnosed as having EEEV on 13th September 2007. He fell ill with the disease on 31st August 2007 just one day after flying home.[http://news.bbc.co.uk/1/hi/scotland/edinburgh_and_east/7033203.stm]

EEEV is closely related to [[Venezuelan equine encephalitis virus]] and [[Western equine encephalitis virus]].

==Gallery==

<gallery>

Image: Alphavirus11.jpeg| Electron micrograph of the Eastern Equine Encephalitis virus in a mosquito salivary gland; Alphavirus. ''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref>

Image: Alphavirus09.jpeg| Transmission electron micrograph (TEM) depicts a salivary gland that had been extracted from a mosquito infected by the Eastern equine encephalitis (EEE) virus, colorized red (83900x mag). ''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref>
Image: Alphavirus07.jpeg| Transmission electron micrograph (TEM) reveals presence of a number of Eastern Equine Encephalitis (EEE) virus virions from a specimen of central nervous system tissue. ''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref>

Image: Alphavirus05.jpeg| Transmission electron micrograph (TEM) revealed the presence of a number of Eastern Equine Encephalitis (EEE) virus virions that happened to be in a specimen of central nervous system tissue. ''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref>

</gallery>

==References==
{{reflist|2}}
*Recent case of Triple E, causing (possibly permanent) coma [http://news.bbc.co.uk/2/hi/uk_news/scotland/edinburgh_and_east/7033203.stm]
*The CDC web page with more complete information:[http://www.cdc.gov/ncidod/dvbid/arbor/eeefact.htm]
*Source for a portion of this information: Evans, Borton, Hintz, Van Vleck. ''The Horse''. 1977. W.H. Freeman and Company. New York.

[[Category:Horse diseases]]
[[Category:Togaviruses]]
[[Category:Animal virology]]

[[de:Östliche Pferdeenzephalomyelitis#Erreger]]
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Desmoplastic small round cell tumor

2016-04-21T12:39:39Z

Sergekorjian:

__NOTOC__
{{SI}}
{{CMG}}{{AE}}{{SR}}

{{SK}} Desmoplastic small round cell tumour; Desmoplastic small round blue cell tumor; Desmoplastic small round blue cell tumour; Intraabdominal desmoplastic small round blue cell tumor; Desmoplastic small cell tumor; Desmoplastic cancer; Desmoplastic sarcoma; DSRCT; Mesothelioblastoma; Polyphenotypic small round cell tumor

==Overview==
Desmoplastic small round cell tumor is an extremely rare, highly aggressive, and malignant neoplasm initially reported by Gerald and Rosai in 1989. The pathogenesis or histogenesis of desmoplastic small round cell tumor is uncertain; it mainly occurs in adolescents and mostly involves the abdominal and/or pelvic peritoneum. Moreover, it was also reported in [[epididymis]], [[pleura]], soft tissues, [[bone]], [[ovary]], and [[kidney]]. The diagnosis can be confirmed by histological and immunohistochemistry studies. CT scan is the most widely used diagnostic modality; abdominopelvic site was the commonest presentation and the disease can occur at other nonserosal surfaces also. Despite multimodality treatments, optimal treatment strategies remain controversial and the prognosis is poor. Current multimodality treatment rarely achieves cure and prolongs life. Here, we described 12 cases of abdominal DSRCT and retrospectively analyzed its clinical, radiological, and biopathological features, highlighting the modalities of treatment.<ref name="ZhangLiu2014">{{cite journal|last1=Zhang|first1=Guangzhao|last2=Liu|first2=Guangjun|last3=Zhao|first3=Dahua|last4=Cui|first4=Xijun|last5=Li|first5=Gang|title=Desmoplastic Small Round Cell Tumor of the Abdomen and Pelvis: Clinicopathological Characters of 12 Cases|journal=The Scientific World Journal|volume=2014|year=2014|pages=1–7|issn=2356-6140|doi=10.1155/2014/549612}}</ref>

==Historical Perspective==
Desmoplastic small round cell tumor was first described by pathologists, William L. Gerald and Juan Rosai, in 1989.<ref name="ZhangLiu2014">{{cite journal|last1=Zhang|first1=Guangzhao|last2=Liu|first2=Guangjun|last3=Zhao|first3=Dahua|last4=Cui|first4=Xijun|last5=Li|first5=Gang|title=Desmoplastic Small Round Cell Tumor of the Abdomen and Pelvis: Clinicopathological Characters of 12 Cases|journal=The Scientific World Journal|volume=2014|year=2014|pages=1–7|issn=2356-6140|doi=10.1155/2014/549612}}</ref>

==Pathophysiology==
===Pathogenesis===
Desmoplastic small round cell tumor is a highly aggressive, rare tumor of mesenchymal origin whose oncogenic effect is presumed to originate from the unique chromosomal translocation t(11;22)(p13:q12), leading to the fusion of the N-terminal domain of Ewing’s sarcoma gene ''[[Ewing sarcoma breakpoint region 1|EWS]]'', to the C-terminal domain of Wilms’ tumor suppressor gene, ''[[WT1]]'', which is found in most but not all desmoplastic small round cell tumors.<ref name="LettieriGarcia-Filion2014">{{cite journal|last1=Lettieri|first1=Christina K.|last2=Garcia-Filion|first2=Pamela|last3=Hingorani|first3=Pooja|title=Incidence and Outcomes of Desmoplastic Small Round Cell Tumor: Results from the Surveillance, Epidemiology, and End Results Database|journal=Journal of Cancer Epidemiology|volume=2014|year=2014|pages=1–5|issn=1687-8558|doi=10.1155/2014/680126}}</ref>

===Genetics===
Desmoplastic small round cell tumor is associated with a unique chromosomal translocation t(11;22)(p13:q12), resulting in an ''[[Ewing sarcoma breakpoint region 1|EWS]]''/''[[WT1]]'' transcript that is diagnostic of this tumor. This transcript codes for a protein that acts as a transcriptional activator that fails to suppress tumor growth. The ''[[Ewing sarcoma breakpoint region 1|EWS]]''/''[[WT1]]'' translocation product targets [[SLC29A4|ENT4]]. ENT4 is also known as [[SLC29A4|PMAT]].<ref name=causesdsrct1>Causes of desmoplastic small round cell tumor. Wikipedia 2016. https://en.wikipedia.org/wiki/Desmoplastic_small-round-cell_tumor#Differential_Diagnoses. Accessed on March 29, 2016</ref>

===Associated Conditions===
There may be a chimeric relationship between desmoplastic small round cell tumor, and [[Wilms' tumor]] and [[Ewing's sarcoma]]. Together with [[neuroblastoma]] and [[non-Hodgkin's lymphoma]], they form the small cell tumors.<ref name=causesdsrct1>Causes of desmoplastic small round cell tumor. Wikipedia 2016. https://en.wikipedia.org/wiki/Desmoplastic_small-round-cell_tumor#Differential_Diagnoses. Accessed on March 29, 2016</ref>

===Gross Pathology===
*On gross pathology, desmoplastic small giant cell tumor is characterized by a mass demonstrating the presence of nonuniform white-gray multinodules, distributed widely in the peritoneum.<ref name="ZhangLiu2014">{{cite journal|last1=Zhang|first1=Guangzhao|last2=Liu|first2=Guangjun|last3=Zhao|first3=Dahua|last4=Cui|first4=Xijun|last5=Li|first5=Gang|title=Desmoplastic Small Round Cell Tumor of the Abdomen and Pelvis: Clinicopathological Characters of 12 Cases|journal=The Scientific World Journal|volume=2014|year=2014|pages=1–7|issn=2356-6140|doi=10.1155/2014/549612}}</ref>
*Desmoplastic small round cell tumor tends to grow along a serosal lining, most commonly the [[peritoneum|peritoneal surface]], but other primary sites have been described.<ref name="LettieriGarcia-Filion2014">{{cite journal|last1=Lettieri|first1=Christina K.|last2=Garcia-Filion|first2=Pamela|last3=Hingorani|first3=Pooja|title=Incidence and Outcomes of Desmoplastic Small Round Cell Tumor: Results from the Surveillance, Epidemiology, and End Results Database|journal=Journal of Cancer Epidemiology|volume=2014|year=2014|pages=1–5|issn=1687-8558|doi=10.1155/2014/680126}}</ref>

===Microscopic Pathology===
On microscopic histopathological analysis, desmoplastic small round cell tumor is characterized by:<ref name=microdsrct1>icroscopic features of desmoplastic small round cell tumour. Libre pathology 2016. https://librepathology.org/wiki/Desmoplastic_small_round_cell_tumour. Accessed on March 30, 2016</ref><ref name="KisO'Regan2012">{{cite journal|last1=Kis|first1=B|last2=O'Regan|first2=K N|last3=Agoston|first3=A|last4=Javery|first4=O|last5=Jagannathan|first5=J|last6=Ramaiya|first6=N H|title=Imaging of desmoplastic small round cell tumour in adults|journal=The British Journal of Radiology|volume=85|issue=1010|year=2012|pages=187–192|issn=0007-1285|doi=10.1259/bjr/57186741}}</ref>
*Broad bands of paucicellular fibrous stroma
*Small round cells in nests with an undulating sharp border
:*The small round cells lack distinct [[nucleoli]] and have scant [[cytoplasm]]; they are small round cell tumor cells.
*[[mitoses|Abundant mitoses]]
*+/-[[Necrosis]]
*Hyperplastic blood vessels

====Gallery====
<gallery>
Image:Desmoplastic small round cell tumour - intermed mag.jpg|Micrograph of a desmoplastic small round cell tumor, showing the characteristic desmoplastic stroma and angulated nests of small round cells on H&E stain.<ref name=microscopicimagedsrct1>Desmoplastic small round cell tumor. Wikipedia 2016. Accessed on March 29, 2016</ref>
Image:Dsrct1.jpg|Display of small round blue cells characteristic of desmoplastic small-round-cell tumor.<ref name=microscopicimagedsrct1>Desmoplastic small round cell tumor. Wikipedia 2016. Accessed on March 29, 2016</ref>
Image:Dsrct2.jpg|Cell exhibiting blue oval and round shapes of desmoplastic small round blue cell tumor.<ref name=microscopicimagedsrct1>Desmoplastic small round cell tumor. Wikipedia 2016. Accessed on March 29, 2016</ref>

</gallery>

===Immunohistochemistry===
Desmoplastic small round cell tumor is demonstrated by positivity to tumor markers, such as:<ref name=microdsrct1>icroscopic features of desmoplastic small round cell tumour. Libre pathology 2016. https://librepathology.org/wiki/Desmoplastic_small_round_cell_tumour. Accessed on March 30, 2016</ref><ref name="ZhangLiu2014">{{cite journal|last1=Zhang|first1=Guangzhao|last2=Liu|first2=Guangjun|last3=Zhao|first3=Dahua|last4=Cui|first4=Xijun|last5=Li|first5=Gang|title=Desmoplastic Small Round Cell Tumor of the Abdomen and Pelvis: Clinicopathological Characters of 12 Cases|journal=The Scientific World Journal|volume=2014|year=2014|pages=1–7|issn=2356-6140|doi=10.1155/2014/549612}}</ref>
*[[SLC4A3|AE1/AE3]]
*[[Desmin]]
*[[Vimentin]]
*EMA
*[[neuron-specific enolase|Neuron-specific enolase (NSE)]]
*[[WT1|WT1 (C-terminal)]]
*[[CD57]]

==Causes==
Common causes of desmoplastic small round cell tumor include [[mutation|genetic mutations]]. A [[translocation|chromosomal translocation]], t(11;22)(p13:q12) resulting in an ''[[Ewing sarcoma breakpoint region 1|EWS]]''/''[[WT1]]'' transcript, may result in formation of desmoplastic small round cell tumor. This transcript codes for a protein that acts as a transcriptional activator that fails to suppress tumor growth. The ''[[Ewing sarcoma breakpoint region 1|EWS]]''/''[[WT1]]'' translocation product targets [[SLC29A4|ENT4]]. ENT4 is also known as [[SLC29A4|PMAT]].<ref name=causesdsrct1>Causes of desmoplastic small round cell tumor. Wikipedia 2016. https://en.wikipedia.org/wiki/Desmoplastic_small-round-cell_tumor#Differential_Diagnoses. Accessed on March 29, 2016</ref>

==Differentiating Desmoplastic Small Round Cell Tumor from other Diseases==
*Desmoplastic small round cell tumor in the abdomen may cause gastrointestinal symptoms and mimic other abdominal tumors. So, they must be differentiated from other tumors in the abdomen, such as:<ref name=ddxdsrct1>Differential diagnosis of desmoplastic small round cell tumor. Wikipedia 2016. https://en.wikipedia.org/wiki/Desmoplastic_small-round-cell_tumor#Differential_Diagnoses. Accessed on March 29, 2016</ref>
:*[[Rhabdomyosarcoma]]
:*[[Neuroblastoma]]
:*[[carcinoid|Mesenteric carcinoid]]
*In older patients, desmoplastic small round cell tumor must be differentiated from:<ref name=ddxdsrct1>Differential diagnosis of desmoplastic small round cell tumor. Wikipedia 2016. https://en.wikipedia.org/wiki/Desmoplastic_small-round-cell_tumor#Differential_Diagnoses. Accessed on March 29, 2016</ref><ref name=radiopaediaddxdsrct2>Differential diagnosis of desmoplastic small round cell tumour. Dr Yuranga Weerakkody and Dr Ayush Goel et al. Radiopaedia 2016. http://radiopaedia.org/articles/desmoplastic-small-round-cell-tumour. Accessed on March 29, 2016</ref>
:*[[Non-Hodgkins lymphoma]]
:*[[Peritoneal mesothelioma]]
:*[[Peritoneal carcinomatosis]]
*In males, desmoplastic small round cell tumor may be mistaken for [[testicular cancer|testicular germ cell tumor]] while in females, desmoplastic small round cell tumor may be mistaken for [[ovarian cancer]].<ref name=ddxdsrct1>Differential diagnosis of desmoplastic small round cell tumor. Wikipedia 2016. https://en.wikipedia.org/wiki/Desmoplastic_small-round-cell_tumor#Differential_Diagnoses. Accessed on March 29, 2016</ref>
*Desmoplastic small round cell tumor must be differentiated from other small-round blue cell cancers, such as:<ref name=ddxdsrct1>Differential diagnosis of desmoplastic small round cell tumor. Wikipedia 2016. https://en.wikipedia.org/wiki/Desmoplastic_small-round-cell_tumor#Differential_Diagnoses. Accessed on March 29, 2016</ref><ref name=smallroundbluecelltumours1>Small round blue cell tumours. Dr Yuranga Weerakkody and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/small-round-blue-cell-tumours. Accessed on March 29, 2016</ref>
:*[[Ewing sarcoma]]
:*[[Neuroblastoma]]
:*[[rhabdomyosarcoma|Embryonal rhabdomyosarcoma]]
:*[[Pineoblastoma]]
:*[[Wilms tumor]]
:*[[Retinoblastoma]]
:*[[Hepatoblastoma]]
:*[[PNET|CNS primitive neuroectodermal tumor (CNS-PNET)]]
:*[[PNET|Peripheral primitive neuroectodermal tumor (pPNET)]]
:*Askin tumor
:*Neuroepithelioma
:*[[Acute leukemia]]
:*[[mesothelioma|Small cell mesothelioma]]

==Epidemiology and Demographics==
===Incidence===
*Age-adjusted incidence rate of desmoplastic small round cell tumor for African Americans and Caucasians is 0.05 and 0.02 per 100,000 individuals, respectively.<ref name="LettieriGarcia-Filion2014">{{cite journal|last1=Lettieri|first1=Christina K.|last2=Garcia-Filion|first2=Pamela|last3=Hingorani|first3=Pooja|title=Incidence and Outcomes of Desmoplastic Small Round Cell Tumor: Results from the Surveillance, Epidemiology, and End Results Database|journal=Journal of Cancer Epidemiology|volume=2014|year=2014|pages=1–5|issn=1687-8558|doi=10.1155/2014/680126}}</ref>
*The overall age-adjusted incidence rate of desmoplastic small round cell tumor is 0.03 per 100,000 individuals, with a peak incidence of 0.074 per 100,000 individuals in the 20–24 years of age group.<ref name="LettieriGarcia-Filion2014">{{cite journal|last1=Lettieri|first1=Christina K.|last2=Garcia-Filion|first2=Pamela|last3=Hingorani|first3=Pooja|title=Incidence and Outcomes of Desmoplastic Small Round Cell Tumor: Results from the Surveillance, Epidemiology, and End Results Database|journal=Journal of Cancer Epidemiology|volume=2014|year=2014|pages=1–5|issn=1687-8558|doi=10.1155/2014/680126}}</ref>

===Age===
*Desmoplastic small round cell tumor is a rare disease that tends to affect children and young adults.
*Peak age of incidence for desmoplastic small round cell tumor is between 20 and 24 years.<ref name="LettieriGarcia-Filion2014">{{cite journal|last1=Lettieri|first1=Christina K.|last2=Garcia-Filion|first2=Pamela|last3=Hingorani|first3=Pooja|title=Incidence and Outcomes of Desmoplastic Small Round Cell Tumor: Results from the Surveillance, Epidemiology, and End Results Database|journal=Journal of Cancer Epidemiology|volume=2014|year=2014|pages=1–5|issn=1687-8558|doi=10.1155/2014/680126}}</ref>

===Gender===
Males are more commonly affected with desmoplastic small round cell tumor than females. The male to female ratio is approximately 4 to 1.<ref name="LettieriGarcia-Filion2014">{{cite journal|last1=Lettieri|first1=Christina K.|last2=Garcia-Filion|first2=Pamela|last3=Hingorani|first3=Pooja|title=Incidence and Outcomes of Desmoplastic Small Round Cell Tumor: Results from the Surveillance, Epidemiology, and End Results Database|journal=Journal of Cancer Epidemiology|volume=2014|year=2014|pages=1–5|issn=1687-8558|doi=10.1155/2014/680126}}</ref>

===Race===
Desmoplatic small round cell tumor usually affects individuals of the African American and Caucasian race. Latin American and Asian individuals are less likely to develop desmoplatic small round cell tumor.<ref name="LettieriGarcia-Filion2014">{{cite journal|last1=Lettieri|first1=Christina K.|last2=Garcia-Filion|first2=Pamela|last3=Hingorani|first3=Pooja|title=Incidence and Outcomes of Desmoplastic Small Round Cell Tumor: Results from the Surveillance, Epidemiology, and End Results Database|journal=Journal of Cancer Epidemiology|volume=2014|year=2014|pages=1–5|issn=1687-8558|doi=10.1155/2014/680126}}</ref>
====Gallery====
[[Image:Gender and race DSRCT.PNG|500px]] (a) Overall age-adjusted incidence of desmoplastic small round cell tumor, (b) Sex-based age-adjusted incidence of desmoplastic small round cell tumor. Males are more likely than females to get desmoplastic small round cell tumor, (c) Race-based, age-adjusted incidence of DSRCT. African Americans are more likely than Caucasians to get desmoplastic small round cell tumor.<ref name="LettieriGarcia-Filion2014">{{cite journal|last1=Lettieri|first1=Christina K.|last2=Garcia-Filion|first2=Pamela|last3=Hingorani|first3=Pooja|title=Incidence and Outcomes of Desmoplastic Small Round Cell Tumor: Results from the Surveillance, Epidemiology, and End Results Database|journal=Journal of Cancer Epidemiology|volume=2014|year=2014|pages=1–5|issn=1687-8558|doi=10.1155/2014/680126}}</ref>

===Demographics===
[[Image:DSRCT.jpg|600px]] Adapted from Christina K. Lettieri et al.<ref name="LettieriGarcia-Filion2014">{{cite journal|last1=Lettieri|first1=Christina K.|last2=Garcia-Filion|first2=Pamela|last3=Hingorani|first3=Pooja|title=Incidence and Outcomes of Desmoplastic Small Round Cell Tumor: Results from the Surveillance, Epidemiology, and End Results Database|journal=Journal of Cancer Epidemiology|volume=2014|year=2014|pages=1–5|issn=1687-8558|doi=10.1155/2014/680126}}</ref>

==Risk Factors==
There are no established risk factors for desmoplastic small round cell tumor.<ref name=riskfactorsdesmoplaticsmallroundcelltumor1>Causes of desmoplastic small round cell tumor. Wikipedia 2016. https://en.wikipedia.org/wiki/Desmoplastic_small-round-cell_tumor. Accessed on March 29, 2016</ref>

==Natural History, Complications, and Prognosis==
===Natural History===
Because the disease can be misdiagnosed or remain undetected, tumors frequently grow large within the abdomen and metastasize or seed to other parts of the body.<ref name="Hayes-JordanAnderson2011">{{cite journal|last1=Hayes-Jordan|first1=Andrea|last2=Anderson|first2=Peter M|title=The diagnosis and management of desmoplastic small round cell tumor: a review|journal=Current Opinion in Oncology|volume=23|issue=4|year=2011|pages=385–389|issn=1040-8746|doi=10.1097/CCO.0b013e3283477aab}}</ref>

===Complications===
Complication sof desmoplastic small round cell tumor include:<ref name="NabiSaste2015">{{cite journal|last1=Nabi|first1=Shahzaib|last2=Saste|first2=Abhijit|last3=Gulati|first3=Rohit|title=A Rare Case of Metastatic Desmoplastic Small Round Cell Tumour: Diagnosis and Management|journal=Case Reports in Oncological Medicine|volume=2015|year=2015|pages=1–6|issn=2090-6706|doi=10.1155/2015/925453}}</ref><ref name=radiographicftrsdsrct1>Radiographic features of desmoplastic small round cell tumour. Dr Yuranga Weerakkody and Dr Ayush Goel et al. Radioipaedia 2016. http://radiopaedia.org/articles/desmoplastic-small-round-cell-tumour. Accessed on March 29, 2016</ref>
*[[peritoneum|Peritoneal seeding]]
*[[Lymph node|Lymph nodal involvement]]
*[[Metastasis]] ([[liver mass|liver]], [[bone mass|bone]], [[lung mass|lung]])

===Prognosis===
*The prognosis for desmoplastic small round cell tumor remains poor and depends upon the stage of the cancer.
*The 5-year overall survival rate of patients with desmoplastic small round cell tumor is approximately 15%.<ref name="Hayes-JordanAnderson2011">{{cite journal|last1=Hayes-Jordan|first1=Andrea|last2=Anderson|first2=Peter M|title=The diagnosis and management of desmoplastic small round cell tumor: a review|journal=Current Opinion in Oncology|volume=23|issue=4|year=2011|pages=385–389|issn=1040-8746|doi=10.1097/CCO.0b013e3283477aab}}</ref>

====Gallery====
[[Image:Prognosis DSRCT.PNG|600px]] (a) Race-based survival of desmoplastic small round cell tumor. There may be a survival disadvantage for African americans compared to Caucasians. Although it did not reach statistical significance, this analysis suggests that African americans are 33% more likely to succumb to desmoplastic small round cell tumor than are Caucasians, (b) Treatment-based survival of desmoplastic small round cell tumor, radiation versus no radiation. There was no statistically significant difference in survival amongst patients who received radiation therapy compared to those who did not, (c) Treatment-based survival of demsoplastic small round cell tumor, radiation after surgery versus no radiation. Patients who received radiation following surgery fared better than those patients who did not. 
Adapted from Christina K. Lettieri et al.<ref name="LettieriGarcia-Filion2014">{{cite journal|last1=Lettieri|first1=Christina K.|last2=Garcia-Filion|first2=Pamela|last3=Hingorani|first3=Pooja|title=Incidence and Outcomes of Desmoplastic Small Round Cell Tumor: Results from the Surveillance, Epidemiology, and End Results Database|journal=Journal of Cancer Epidemiology|volume=2014|year=2014|pages=1–5|issn=1687-8558|doi=10.1155/2014/680126}}</ref>

==Diagnosis==
===Symptoms===
*There are few early warning signs that a patient has a desmoplastic small round cell tumor.
*Patients are often young and healthy as the tumors grow and spread uninhibited within the abdominal cavity. These are rare tumors and the symptoms are often misdiagnosed by physicians. The abdominal lump may grow to enormous size before being noticed by the patient.<ref name=smdsrct1>Symptoms of desmoplastic small round cell tumor. Wikipedia 2016. https://en.wikipedia.org/wiki/Desmoplastic_small-round-cell_tumor#Differential_Diagnoses. Accessed on March 29, 2016</ref>

====Common Symptoms====
Common symptoms of desmoplastic small round cell tumor include:<ref name=smdsrct1>Symptoms of desmoplastic small round cell tumor. Wikipedia 2016. https://en.wikipedia.org/wiki/Desmoplastic_small-round-cell_tumor#Differential_Diagnoses. Accessed on March 29, 2016</ref><ref name="ZhangLiu2014">{{cite journal|last1=Zhang|first1=Guangzhao|last2=Liu|first2=Guangjun|last3=Zhao|first3=Dahua|last4=Cui|first4=Xijun|last5=Li|first5=Gang|title=Desmoplastic Small Round Cell Tumor of the Abdomen and Pelvis: Clinicopathological Characters of 12 Cases|journal=The Scientific World Journal|volume=2014|year=2014|pages=1–7|issn=2356-6140|doi=10.1155/2014/549612}}</ref>
*[[Abdominal distention]]
*[[Abdominal mass|Lump in abdomen]]
*[[Abdominal pain]]
*[[Vomiting]]
*[[Back pain]]
*[[intestinal obstruction|Gastrointestinal obstruction]]
*[[anorexia|Lack of appetite]]
*[[Fatigue]]
*[[Weakness]]
*[[Cachexia]]

====Less Common Symptoms====
Less common symptoms of desmoplastic small round cell tumor include:<ref name=smdsrct1>Symptoms of desmoplastic small round cell tumor. Wikipedia 2016. https://en.wikipedia.org/wiki/Desmoplastic_small-round-cell_tumor#Differential_Diagnoses. Accessed on March 29, 2016</ref>
*[[lump|Unknown lumps]]
*[[thyroid gland|Thyroid conditions]]
*[[endocrinology|Hormonal problems]]
*[[Blood clotting|Blood clotting problems]]
*[[renal disease|Kidney or urological problems]]
*Lump in the [[testicle]], [[breast]], [[uterus]], [[Vestibule of the vagina|vagina]], or [[ovary]]

===Physical Examination===
Common physical examination findings of desmoplastic small round cell tumor include:<ref name="KisO'Regan2012">{{cite journal|last1=Kis|first1=B|last2=O'Regan|first2=K N|last3=Agoston|first3=A|last4=Javery|first4=O|last5=Jagannathan|first5=J|last6=Ramaiya|first6=N H|title=Imaging of desmoplastic small round cell tumour in adults|journal=The British Journal of Radiology|volume=85|issue=1010|year=2012|pages=187–192|issn=0007-1285|doi=10.1259/bjr/57186741}}</ref><ref name="ZhangLiu2014">{{cite journal|last1=Zhang|first1=Guangzhao|last2=Liu|first2=Guangjun|last3=Zhao|first3=Dahua|last4=Cui|first4=Xijun|last5=Li|first5=Gang|title=Desmoplastic Small Round Cell Tumor of the Abdomen and Pelvis: Clinicopathological Characters of 12 Cases|journal=The Scientific World Journal|volume=2014|year=2014|pages=1–7|issn=2356-6140|doi=10.1155/2014/549612}}</ref>
*[[abdominal mass|Palpable adominal mass]]
*[[Ascites]]
*Increased abdominal girth

===CT===
*Abdominal CT scan is the most widely used diagnostic modality for desmoplastic small round cell tumor.<ref name="ZhangLiu2014">{{cite journal|last1=Zhang|first1=Guangzhao|last2=Liu|first2=Guangjun|last3=Zhao|first3=Dahua|last4=Cui|first4=Xijun|last5=Li|first5=Gang|title=Desmoplastic Small Round Cell Tumor of the Abdomen and Pelvis: Clinicopathological Characters of 12 Cases|journal=The Scientific World Journal|volume=2014|year=2014|pages=1–7|issn=2356-6140|doi=10.1155/2014/549612}}</ref>
*Findings on CT scan suggestive of desmoplastic small round cell tumor include a solitary to multiple soft tissue masses with no definite organ of origin, usually in the retrovesical or rectouterine space, which enhance heterogenously on contrast studies. [[Necrosis]], [[hemorrhage]], and [[fibrosis|fibrous components]] are common.
*[[peritoneum|Peritoneal seeding]], [[lymph node|lymph nodal involvement]], [[metastasis|liver and bone metastases]] may also be demonstrated.<ref name=radiographicftrsdsrct1>Radiographic features of desmoplastic small round cell tumour. Dr Yuranga Weerakkody and Dr Ayush Goel et al. Radioipaedia 2016. http://radiopaedia.org/articles/desmoplastic-small-round-cell-tumour. Accessed on March 29, 2016</ref>

====Gallery====
<gallery>
Image:Ct image dsrct.jpg|Abdominopelvic CT scan revealed diffuse multiple soft-tissue masses in peritoneal and mesenteric surfaces.<ref name="ZhangLiu2014">{{cite journal|last1=Zhang|first1=Guangzhao|last2=Liu|first2=Guangjun|last3=Zhao|first3=Dahua|last4=Cui|first4=Xijun|last5=Li|first5=Gang|title=Desmoplastic Small Round Cell Tumor of the Abdomen and Pelvis: Clinicopathological Characters of 12 Cases|journal=The Scientific World Journal|volume=2014|year=2014|pages=1–7|issn=2356-6140|doi=10.1155/2014/549612}}</ref>
Image:Ct image 2 dsrct.jpg|Contrast-enhanced CT revealed the heterogeneous mass with obvious enhancement areas and scattered low attenuation.<ref name="ZhangLiu2014">{{cite journal|last1=Zhang|first1=Guangzhao|last2=Liu|first2=Guangjun|last3=Zhao|first3=Dahua|last4=Cui|first4=Xijun|last5=Li|first5=Gang|title=Desmoplastic Small Round Cell Tumor of the Abdomen and Pelvis: Clinicopathological Characters of 12 Cases|journal=The Scientific World Journal|volume=2014|year=2014|pages=1–7|issn=2356-6140|doi=10.1155/2014/549612}}</ref>

</gallery>

===MRI===
*MRI may helpful in delineating the extent of desmoplastic small round cell tumor, if surgery is considered.<ref name="KisO'Regan2012">{{cite journal|last1=Kis|first1=B|last2=O'Regan|first2=K N|last3=Agoston|first3=A|last4=Javery|first4=O|last5=Jagannathan|first5=J|last6=Ramaiya|first6=N H|title=Imaging of desmoplastic small round cell tumour in adults|journal=The British Journal of Radiology|volume=85|issue=1010|year=2012|pages=187–192|issn=0007-1285|doi=10.1259/bjr/57186741}}</ref>
*On MRI, desmoplastic small round cell tumor is characterized by hypo- to isointensity on T1-weighted images. On contrast administration, it has a heterogenous enhancement, due to the fibrous stroma and degenerative features including [[necrosis]], [[hemorrhage]], and [[calcification].<ref name="KisO'Regan2012">{{cite journal|last1=Kis|first1=B|last2=O'Regan|first2=K N|last3=Agoston|first3=A|last4=Javery|first4=O|last5=Jagannathan|first5=J|last6=Ramaiya|first6=N H|title=Imaging of desmoplastic small round cell tumour in adults|journal=The British Journal of Radiology|volume=85|issue=1010|year=2012|pages=187–192|issn=0007-1285|doi=10.1259/bjr/57186741}}</ref>

==Treatment==
*Desmoplastic small round cell tumor is frequently misdiagnosed. Adult patients should always be referred to a sarcoma specialist. This is an aggressive, rare, fast spreading tumor and both pediatric and adult patients should be treated at a sarcoma center.<ref name=rxofdsrct1>Treatment of desmoplastic small round cell tumor. Wikipedia 2016. https://en.wikipedia.org/wiki/Desmoplastic_small-round-cell_tumor. Accessed on March 30, 2016</ref>
*[[surgery|Surgical excision]] with [[combination chemotherapy]] as an adjunct is mandatory for nonmetastatic cases because these modalities used in isolation may have less impact.<ref name="ZhangLiu2014">{{cite journal|last1=Zhang|first1=Guangzhao|last2=Liu|first2=Guangjun|last3=Zhao|first3=Dahua|last4=Cui|first4=Xijun|last5=Li|first5=Gang|title=Desmoplastic Small Round Cell Tumor of the Abdomen and Pelvis: Clinicopathological Characters of 12 Cases|journal=The Scientific World Journal|volume=2014|year=2014|pages=1–7|issn=2356-6140|doi=10.1155/2014/549612}}</ref>
*There is no standard protocol for desmoplastic small round cell tumor; however, recent journals and studies have reported that some patients respond to high-dose (P6 Protocol) [[chemotherapy]], maintenance chemotherapy, [[debulking procedure]], [[cytoreductive surgery]], and [[radiotherapy|radiation therapy]].
*Other treatment options for desmoplastic small round cell tumor include [[stem cell transplant|hematopoietic stem cell transplantation]], intensity-modulated radiation Therapy, [[radiofrequency ablation]], stereotactic body radiation therapy, intraperitoneal hyperthermic chemoperfusion, and clinical trials.

==References==
{{reflist|2}}

[[Category:Types of cancer]]
[[Category:Oncology]]
[[Category:Disease]]

{{WS}}
{{WH}}

Eastern equine encephalitis

2016-04-20T15:04:10Z

Sergekorjian:

__NOTOC__
{{SI}}
{{CMG}} {{AE}} {{AG}}

{{SK}} EEE; EEEV; East equine encephalitis; Triple E

==Overview==
Eastern equine encephalitis is a moderate to severe infection of the [[central nervous system]]. Eastern equine encephalitis belongs to the Group IV positive-sense ssRNA virus within the ''[[Togaviridae]]'' family of viruses, and the genus ''[[Alphavirus]]''. Eastern equine encephalitis is closely related to [[western equine encephalitis]] and [[Venezuelan equine encephalitis]]. Eastern equine encephalitis virus is usually transmitted via [[mosquito]]s to the human host, primarily ''Culiseta melanura''. Eastern equine encephalitis virus must be differentiated from other diseases that cause [[fever]], [[headache]], [[seizures]], and [[altered mental status]]. There are approximately 8 human cases of eastern equine encephalitis annually in the United States, most commonly affecting children under the age of 15 and adults over the age of 50. Prognosis for eastern equine encephalitis is generally poor. Approximately 33% of patients progress to [[mortality]], and approximately 50% of surviving patients have mild to severe [[neurodegenerative]] losses and [[seizures]]. The diagnostic method of choice for eastern equine encephalitis virus is laboratory testing. There is no treatment for eastern equine encephalitis virus; the mainstay of therapy is supportive care. There are currently no human [[vaccine]]s available for eastern equine encephalitis.

==Historical Perspective==
In 1831, eastern equine encephalitis virus was first reported in Massachusetts, USA following the sudden death of 75 horses, which died mysteriously of viral encephalitis. In 1938, the earliest evidence of eastern equine encephalitis virus activity in Canada was reported in the Ontario cities of St. George and St. Catharines.<ref name=EEEVHP1> Schofield F, Labzoffsky N. Report on cases of suspected encephalomyelitis occurring in the vicinity of St. George. Rep Ont Dept Agric OVC. 193829:25-29. </ref><ref name="pmid7757923">{{cite journal| author=Carman PS, Artsob H, Emery S, Maxie MG, Pooley D, Barker IK et al.| title=Eastern equine encephalitis in a horse from southwestern Ontario. | journal=Can Vet J | year= 1995 | volume= 36 | issue= 3 | pages= 170-2 | pmid=7757923 | doi= | pmc=PMC1686920 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7757923 }} </ref>

==Classification==
Eastern equine encephalitis may be classified according to location of the disease into 2 subtypes: systemic or encephalitic. Eastern equine encephalitis may also be classified according to [[invasive|neuroinvasiveness]] of the disease into 2 subtypes: neuroinvasive and non-neuroinvasive. Eastern equine encephalitis belongs to the Group IV positive-sense ssRNA virus within the ''[[Togaviridae]]'' family of viruses, and the genus ''[[Alphavirus]]''. Eastern equine encephalitis is closely related to [[western equine encephalitis]] virus and [[Venezuelan equine encephalitis]] virus. Eastern equine encephalitis is known as an [[arbovirus]], or an arthropod-borne virus.

==Pathophysiology==
Eastern equine encephalitis virus is usually transmitted via [[mosquito]]s to the human host. Eastern equine encephalitis virus contains [[positive-sense ssRNA virus|positive-sense]] viral [[RNA]]; this RNA has its genome directly utilized as if it were mRNA, producing a single protein which is modified by host and viral proteins to form the various proteins needed for [[replication]]. The following table is a summary of the eastern equine encephalitis virus:<ref name=ViralZoneAlpha> Alphavirus. SIB Swiss Institute of Bioinformatics. http://viralzone.expasy.org/viralzone/all_by_species/625.html Accessed on March 15, 2016 </ref>
{| class="wikitable"
! style="text-align: center; font-weight: bold;" | Characteristic
! style="text-align: center; font-weight: bold;" | Data
|-
| Nucleic acid
| [[RNA]]
|-
| Sense
| [[positive-sense ssRNA virus|ssRNA(+)]]
|-
| Virion
| [[enveloped virus|Enveloped]]
|-
| [[Capsid]]
| Spherical
|-
| Symmetry
| Yes; T=4 [[icosahedral]]
|-
| Capsid [[monomers]]
| 240
|-
| Monomer length (diameter)
| 65-70 nm
|-
| Additional envelope information
| 80 spikes; each spike is a [[trimer]] of E1/E2 proteins
|-
| Genome shape
| Linear
|-
| Genome length
| 11-12 kb
|-
| [[Nucleotide]] cap
| Yes
|-
| [[Polyadenylation|Polyadenylated]] tail
| Yes
|-
| [[Incubation period]]
| 4-10 days
|}

Eastern equine encephalitis is contracted by the [[bite]] of an infected [[mosquito]], primarily ''Culiseta melanura''. The virus is maintained in a cycle between ''Culiseta melanura'' mosquitos and avian hosts in [[freshwater]] hardwood swamps. ''Culiseta melanura'' is not an important vector of eastern equine virus to humans because it feeds almost exclusively on birds. Transmission to humans requires mosquito species capable of creating a "bridge" between infected birds and uninfected mammals, such as some ''[[Aedes]]'', ''Coquillettidia'', and ''Culex'' species. The [[incubation period]] is 4-10 days.<ref name=CDCEEE> Eastern Equine Encephalitis. CDC. http://www.cdc.gov/EasternEquineEncephalitis/index.html Accessed on March 15, 2016 </ref> Humans and horses are dead-end hosts for the virus, meaning there is an insufficient amount of eastern equine encephalitis virus in the blood stream to infect a mosquito. Many cases in horses are fatal. There is no known transmission between horses and humans.<ref name=EEEVILPubHealth> Eastern Equine Encephalitis Virus (EEEV). Illinois Department of Public Health (2010) http://www.idph.state.il.us/public/hb/hb_eee.htm Accessed on March 15, 2016. </ref> Recent studies have demonstrated other equine, such as mules and donkeys, and other animals, such as pigs, reptiles, amphibians, and rodents, can be infected.

Eastern equine encephalitis virus is transmitted in the following pattern:<ref name=ViralZoneAlpha> Alphavirus. SIB Swiss Institute of Bioinformatics. http://viralzone.expasy.org/viralzone/all_by_species/625.html Accessed on March 15, 2016 </ref>

#Attachment of the viral E [[glycoprotein]] to host receptors mediates [[clathrin|clathrin-mediated]] [[endocytosis]] of virus into the host cell.
#Fusion of [[biological membrane|virus membrane]] with the host [[cell membrane]]. RNA genome is released into the [[cytoplasm]].
#The [[positive-sense ssRNA virus]] is [[translate]]d into a [[polyprotein]], which is cleaved into non-structural proteins necessary for RNA synthesis ([[replication]] and [[transcription]]).
#[[Replication]] takes place in [[cytoplasm]]ic viral factories at the surface of [[endosome]]s. A [[dsRNA]] [[genome]] is synthesized from the genomic ssRNA(+).
#The [[dsRNA]] [[genome]] is [[transcribed]] thereby providing viral [[mRNA]]s (new ssRNA(+) genomes).
#Expression of the subgenomic RNA (sgRNA) gives rise to the structural proteins.
#Virus assembly occurs at the [[endoplasmic reticulum]].
#[[Virion]]s bud at the [[endoplasmic reticulum]], are transported to the [[Golgi apparatus]], and then exit the cell via the [[secretory pathway]].

==Causes==
Eastern equine encephalitis may be caused by eastern equine encephalitis virus.

==Differentiating Eastern equine encephalitis from Other Diseases==
Eastern equine encephalitis virus must be differentiated from other diseases that cause [[fever]], [[headache]], [[seizures]], and [[altered mental status]], such as:<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref><ref name="pmid14978145">{{cite journal| author=Kennedy PG| title=Viral encephalitis: causes, differential diagnosis, and management. | journal=J Neurol Neurosurg Psychiatry | year= 2004 | volume= 75 Suppl 1 | issue= | pages= i10-5 | pmid=14978145 | doi= | pmc=PMC1765650 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14978145 }} </ref><ref name=NYDeptofHealth> Arboviral Infections (arthropod-borne encephalitis, eastern equine encephalitis, St. Louis encephalitis, California encephalitis, Powassan encephalitis, West Nile encephalitis). New York State Department of Health (2006). https://www.health.ny.gov/diseases/communicable/arboviral/fact_sheet.htm Accessed on February 23, 2016 </ref>

{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
|+
! style="background: #4479BA; width: 120px;" | {{fontcolor|#FFF|Disease}}
! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|Findings}}
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Meningitis]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Meningitis]] presents with [[headache]], [[altered mental status]], and [[inflammation]] of the [[meninges]], which may develop in the setting of an [[infection]], physical injury, [[cancer]], or certain drugs; it may have an indolent evolution, resolving on its own, or may present as an rapidly evolving [[inflammation]], causing neurologic damage and possible [[mortality]]. {{see also|Bacterial meningitis|Viral meningitis|Fungal meningitis}}
|-
| style="padding: 5px 5px; background: #DCDCDC;" |'''[[Brain abscess]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Brain abscess]] presents with an [[abscess]] in the [[brain]] caused by the [[inflammation]] and accumulation of [[infected]] material from local or remote infectious areas of the body; the infectious agent may also be introduced as a result of head [[trauma]] or [[neurosurgery|neurological procedures]].
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Acute disseminated encephalomyelitis]] (ADEM)'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Acute disseminated encephalomyelitis]] presents with scattered foci of [[demyelination]] and perivenular [[inflammation]]; it can cause focal neurological signs and decreased ability to focus.
|-
|}

==Epidemiology and Demographics==
===Incidence===
There are approximately 8 human cases of eastern equine encephalitis annually in the United States.<ref name=CDCEEE> Eastern Equine Encephalitis. CDC. http://www.cdc.gov/EasternEquineEncephalitis/index.html Accessed on March 15, 2016 </ref>

===Age===
Eastern equine encephalitis commonly affects individuals younger than 15 and older than 50 years of age.<ref name=CDCEEE> Eastern Equine Encephalitis. CDC. http://www.cdc.gov/EasternEquineEncephalitis/index.html Accessed on March 15, 2016 </ref>

===Seasonal===
Eastern equine encephalitis outbreaks have occurred when there is relatively higher rainfall in the late summer and early fall of the previous year and during the current summer of an outbreak.<ref name=EEEOntario> Ontario Agency for Health Protection and Promotion (Public Health Ontario). Eastern equine encephalitis: history and enhanced surveillance in Ontario. Toronto, ON: Queen's Printer for Ontario; 2014. Accessed on March 15, 2016 </ref> Specifically, the risk of contracting eastern equine encephalitis is highest from late July through September, when more mosquitos are present and active.<ref name=EEENYPubHealth> Eastern Equine Encephalitis (EEE). New York State Department of Public Health (2012). https://www.health.ny.gov/diseases/communicable/eastern_equine_encephalitis/fact_sheet.htm Accessed on March 15, 2016.</ref>

===Geographic Location===
The majority of eastern equine encephalitis cases are reported on the East Coast of the United States, specifically in Massachusetts, Florida, and New Jersey. Eastern equine encephalitis virus transmission is most common in and around freshwater hardwood swamps in the Atlantic and Gulf Coast states and the Great Lakes region.<ref name=CDCEEE> Eastern Equine Encephalitis. CDC. http://www.cdc.gov/EasternEquineEncephalitis/index.html Accessed on March 15, 2016 </ref>

Maps regarding geographic distribution of eastern equine encephalitis cases can be found [http://www.cdc.gov/EasternEquineEncephalitis/tech/epi.html here].

==Risk Factors==
Common risk factors in the development of eastern equine encephalitis include:
*[[Age]] (<15 years; >50 years)
*[[Immunosuppression]]
*Residing or visiting woodland areas
*[[Mosquito]] contact
*Bird contact
*Horse contact
*Summer season
*Outdoor recreational activities

==Natural History, Complications, and Prognosis==
===Natural History===
If left untreated, eastern equine encephalitis may cause uncontrolled [[fever]], increased [[intracranial pressure]], and [[seizures]].<ref name="pmid23343480">{{cite journal| author=Silverman MA, Misasi J, Smole S, Feldman HA, Cohen AB, Santagata S et al.| title=Eastern equine encephalitis in children, Massachusetts and New Hampshire,USA, 1970-2010. | journal=Emerg Infect Dis | year= 2013 | volume= 19 | issue= 2 | pages= 194-201; quiz 352 | pmid=23343480 | doi=10.3201/eid1902.120039 | pmc=PMC3559032 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23343480 }} </ref> Eastern equine encephalitis usually clears within 1-2 weeks and rarely recurs; the recovery period is significantly longer.

===Complications===
Common complications of eastern equine encephalitis include:<ref name= NINDS> Meningitis and Encephalitis Fact Sheet. National Institute of Neurological Disorders and Stroke. National Institutes of Health (2015). http://www.ninds.nih.gov/disorders/encephalitis_meningitis/detail_encephalitis_meningitis.htm Accessed on February 9, 2015 </ref>
*Recurring [[seizure]]s
*[[Coma]]
*Loss of basic [[motor skill]]s
*Loss of [[coordination]]
*[[Meningitis]]
*Increased [[intracranial pressure]]
*[[Shock]]
*[[Respiratory failure]]

===Prognosis===
Prognosis for eastern equine encephalitis is generally poor. Approximately 33% of patients progress to [[mortality]].<ref name=CDCEEE> Eastern Equine Encephalitis. CDC. http://www.cdc.gov/EasternEquineEncephalitis/index.html Accessed on March 15, 2016 </ref> Approximately 50% of surviving patients have mild to severe [[neurodegenerative]] losses and [[seizures]].<ref name=EEEMNPubHealth> Eastern Equine Encephalitis. Minnesota Department of Health (2010). http://www.health.state.mn.us/divs/idepc/diseases/eeencephalitis/eee.html Accessed on March 17, 2016. </ref>

==Diagnosis==
===Diagnostic criteria===
Neuroinvasive vs non-neuroinvasive eastern equine encephalitis can be differentiated based on both clinical and laboratory findings. These include:<ref name=WVPubHealth> Arboviral Infection: Surveillance Protocol (2016) West Virginia Department of Health and Human Resources: Bureau of Public Health (2016). http://www.dhhr.wv.gov/oeps/disease/Zoonosis/Mosquito/Documents/arbovirus/arbovirus-protocol.pdf Accessed on March 3, 2016 </ref><ref name=CDCCritArboInvasive> Arboviral diseases, neuroinvasive and non-neuroinvasive 2015 Case Definition. National Notifiable Diseases Surveillance System (NNDSS). Centers for Disease Control (2015). https://wwwn.cdc.gov/nndss/conditions/arboviral-diseases-neuroinvasive-and-non-neuroinvasive/case-definition/2015/ Accessed on March 31, 2016. </ref>

{| class="wikitable"
! style="text-align: center; font-weight: bold;" | Eastern Equine Encephalitis Subtype
! style="text-align: center; font-weight: bold;" | Clinical Presentation
! style="text-align: center; font-weight: bold;" | Laboratory Findings
|-
| style="font-style: italic;" | Neuroinvasive
|
:{{unicode|☑}} [[Meningitis]], [[encephalitis]], acute flaccid [[paralysis]], or other acute signs of central or peripheral neurologic dysfunction, as documented by a [[physician]] '''AND'''
:{{unicode|☑}} Absence of a more likely clinical explanation
|
:{{unicode|☑}} Isolation of [[virus]] from, or demonstration of specific viral [[antigen]] or [[nucleic acid in]], [[tissue]], [[blood]], [[cerebrospinal fluid]] (CSF) '''OR'''
:{{unicode|☑}} Four-fold or greater change in virus-specific quantitative antibody [[titer]]s in paired sera '''OR'''
:{{unicode|☑}} Virus-specific [[IgM]] antibodies in [[serum]] with confirmatory virus-specific neutralizing antibodies in the same or a later specimen '''OR'''
:{{unicode|☑}} Virus-specific [[IgM]] antibodies in [[cerebrospinal fluid]], with or without a reported [[pleocytosis]], and a negative result for other IgM antibodies in cerebrospinal fluid for arboviruses endemic to the region where exposure occurred
|-
| style="font-style: italic;" | Non-neuroinvasive
|
:{{unicode|☑}} [[Fever]] and [[chills]] as reported by the [[patient]] or a [[health care provider]] '''AND'''
:{{unicode|☑}} Absence of [[invasive|neuroinvasive]] disease '''AND'''
:{{unicode|☑}} Absence of a more likely clinical explanation
|
:{{unicode|☑}} Isolation of [[virus]] from, or demonstration of specific viral [[antigen]] or [[nucleic acid]] in, [[tissue]], [[blood]], or other body fluid, excluding [[cerebrospinal fluid]] '''OR'''
:{{unicode|☑}} Four-fold or greater change in virus-specific quantitative antibody [[titer]]s in paired sera '''OR'''
:{{unicode|☑}} Virus-specific [[IgM]] antibodies in [[serum]] with confirmatory virus-specific neutralizing antibodies in the same or a later specimen
|}

===History and Symptoms===
If possible, a detailed and thorough history from the patient is necessary. Common symptoms of eastern equine encephalitis include:<ref name=CDCEEE> Eastern Equine Encephalitis. CDC. http://www.cdc.gov/EasternEquineEncephalitis/index.html Accessed on March 15, 2016 </ref><ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref>
*[[Fever]]
*[[Chills]]
*[[Headache]]
*[[Fatigue]]
*[[myalgia|Muscle pain]]
*[[Dizziness]]
*[[Altered mental status]]

===Physical Examination===
Common physical examination findings of eastern equine encephalitis include:<ref name=EEENYPubHealth> Eastern Equine Encephalitis (EEE). New York State Department of Public Health (2012). https://www.health.ny.gov/diseases/communicable/eastern_equine_encephalitis/fact_sheet.htm Accessed on March 15, 2016.</ref>
*[[Fever]]
*[[Ataxia]]
*[[Seizure]]s
*[[Obtundation]]
*[[Myalgia]]
*[[myelitis|Acute flaccid myelitis]]
*[[Lethargy]]
*[[Meningism]]
*[[Photophobia]]

===Laboratory Findings===
The diagnostic method of choice for eastern equine encephalitis is laboratory testing. Laboratory findings consistent with the diagnosis of eastern equine encephalitis include:<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref>
*[[Serologic]] [[cross-reactivity]]
*Presence of [[IgM]] [[antibody|antibodies]]
*Persistence of [[IgG]] and neutralizing [[antibody|antibodies]]
*Confirmation of arboviral-specific neutralizing antibodies in [[enzyme linked immunosorbent assay (ELISA)]]
*[[Leukocytosis]] with a [[neutrophil]] predominance
*Normal [[glucose]] levels
*[[Hyponatremia]]
*In [[cerebrospinal fluid]]:
**Significant [[pleocytosis]]
**Increased protein levels
**Slightly lower [[glucose]] levels

===CT===
On [[CT]] scan, eastern equine encephalitis is characterized by [[diffuse]] [[cerebral edema]] in 40% of patients.

===MRI===
On [[MRI]], eastern equine encephalitis is characterized by abnormalities in the [[thalamus]], [[basal ganglia]], and [[brainstem]].

===EEG===
On [[EEG]], eastern equine encephalitis is typically diffusely slow with some patients having burst suppression, or diffuse high-voltage [[delta wave]] slowing.

==Treatment==
===Medical Therapy===
There is no treatment for eastern equine encephalitis; the mainstay of therapy is supportive care. Because supportive care is the only treatment for eastern equine encephalitis, physicians often do not request the tests required to specifically identify the eastern equine encephalitis virus.

===Surgery===
Surgical intervention is not recommended for the management of eastern equine encephalitis.

===Prevention===
There is no human vaccine for eastern equine encephalitis. There is an eastern equine encephalitis vaccine available for horses. In consultation with a veterinarian, vaccinate your horse(s) against the virus. Primary prevention strategies for eastern equine encephalitis include:<ref name=EEENYPubHealth> Eastern Equine Encephalitis (EEE). New York State Department of Public Health (2012). https://www.health.ny.gov/diseases/communicable/eastern_equine_encephalitis/fact_sheet.htm Accessed on March 15, 2016.</ref>
*Removal of [[standing water]]
*Screens on doors and windows
*When outdoors, wearing:
**Insect repellent containing [[DEET]]
**Long sleeves, pants; tucking in pants into high socks

==References==
{{reflist|2}}

[[Category:Viruses]]
[[Category:Neurology]]
[[Category:Infectious disease]]

{{WikiDoc Help Menu}}

Venezuelan equine encephalitis

2016-04-20T15:03:16Z

Sergekorjian: /* Differentiating Venezuelan equine encephalitis from Other Diseases */

__NOTOC__
{{SI}}
{{CMG}} {{AE}} {{AG}}

{{SK}} VEE; VEEV; Venezuelan equine encephalitis virus; Venezuelan encephalitis; Venezuelan equine encephalomyelitis; Venezuelan equine fever

==Overview==
Venezuelan equine encephalitis is a mild to moderate, though sometimes [[fatal]], infection of the [[central nervous system]]. Venezuelan equine encephalitis belongs to the Group IV positive-sense ssRNA virus within the ''[[Togaviridae]]'' family of viruses, and the genus ''[[Alphavirus]]''. Venezuelan equine encephalitis virus is usually transmitted via [[mosquito]]s to the human host, primarily ''Culex melanoconion'' or ''[[Aedes]]''. Venezuelan equine encephalitis virus must be differentiated from other diseases that cause [[fever]], [[headache]], [[seizures]], and [[altered mental status]]. Prognosis for Venezuelan equine encephalitis is generally good; less than 1% of patients infected with the Venezuelan equine encephalitis virus present with symptoms. Symptomatic patients often recover within 2-3 weeks of infection. The [[case fatality|case-fatality]] rate of Venezuelan equine encephalitis is approximately 0.7. If possible, a detailed and thorough history from the patient is necessary. If the patient is female, a pregnancy test should be administered to monitor for potential [[miscarriage]]. Venezuelan equine encephalitis is usually asymptomatic. The diagnostic method of choice for Venezuelan equine encephalitis is laboratory testing. There is no treatment for Venezuelan equine encephalitis; the mainstay of therapy is supportive care. There is a vaccination approved for limited use for Venezuelan equine encephalitis, though its effectiveness is often questioned.

==Historical Perspective==
Venezuelan equine encephalitis was first discovered in 1938 after the virus was isolated from the [[brain]]s of dead horses following an outbreak in the Venezuelan countryside.<ref name="pmid17840536">{{cite journal| author=Beck CE, Wyckoff RW| title=VENEZUELAN EQUINE ENCEPHALOMYELITIS. | journal=Science | year= 1938 | volume= 88 | issue= 2292 | pages= 530 | pmid=17840536 | doi=10.1126/science.88.2292.530 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17840536 }} </ref> There have been several outbreaks of Venezuelan equine encephalitis. In 1995, the last major [[outbreak]] occurred in Venezuela and Columbia and resulted in approximately 75,000 cases, of which 3,000 had severe [[neurological]] [[complication]]s and 300 progressed to [[mortality]].<ref name="pmid9086137">{{cite journal| author=Rivas F, Diaz LA, Cardenas VM, Daza E, Bruzon L, Alcala A et al.| title=Epidemic Venezuelan equine encephalitis in La Guajira, Colombia, 1995. | journal=J Infect Dis | year= 1997 | volume= 175 | issue= 4 | pages= 828-32 | pmid=9086137 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9086137 }} </ref> The last reported case of Venezuelan equine encephalitis in the United States occurred in southern Texas in 1972.<ref name=VEEVCanPH1> Venezuelan Equine Encephalomyelitis - Fact Sheet. Canadian Food Inspection Agency (2012). http://www.inspection.gc.ca/animals/terrestrial-animals/diseases/reportable/venezuelan-equine-encephalomyelitis/fact-sheet/eng/1329841926239/1329842048136 Accessed on March 31, 2016. </ref>

==Classification==
Venezuelan equine encephalitis may be classified according to location of the disease into 2 subtypes: systemic or encephalitic. Venezuelan equine encephalitis may also be classified according to [[invasive|neuroinvasiveness]] of the disease into 2 subtypes: neuroinvasive and non-neuroinvasive.<ref name=CDCCritArboInvasive> Arboviral diseases, neuroinvasive and non-neuroinvasive 2015 Case Definition. National Notifiable Diseases Surveillance System (NNDSS). Centers for Disease Control (2015). https://wwwn.cdc.gov/nndss/conditions/arboviral-diseases-neuroinvasive-and-non-neuroinvasive/case-definition/2015/ Accessed on March 31, 2016. </ref> Venezuelan equine encephalitis belongs to the Group IV positive-sense ssRNA virus within the ''[[Togaviridae]]'' family of viruses, and the genus ''[[Alphavirus]]''. Venezuelan equine encephalitis is closely related to [[eastern equine encephalitis]] virus and [[western equine encephalitis]] virus. Venezuelan equine encephalitis is known as an [[arbovirus]], or an arthropod-borne virus.

==Pathophysiology==
Venezuelan equine encephalitis virus is usually transmitted via [[mosquito]]s to the human host. Venezuelan equine encephalitis virus contains [[positive-sense ssRNA virus|positive-sense]] viral [[RNA]]; this RNA has its genome directly utilized as if it were mRNA, producing a single protein which is modified by host and viral proteins to form the various proteins needed for [[replication]]. The following table is a summary of the Venezuelan equine encephalitis virus:<ref name=ViralZoneAlpha> Alphavirus. SIB Swiss Institute of Bioinformatics. http://viralzone.expasy.org/viralzone/all_by_species/625.html Accessed on March 15, 2016 </ref>

{| class="wikitable"
! style="text-align: center; font-weight: bold;" | Characteristic
! style="text-align: center; font-weight: bold;" | Data
|-
| Nucleic acid
| [[RNA]]
|-
| Sense
| [[positive-sense ssRNA virus|ssRNA(+)]]
|-
| Virion
| [[enveloped virus|Enveloped]]
|-
| [[Capsid]]
| Spherical
|-
| Symmetry
| Yes; T=4 [[icosahedral]]
|-
| Capsid [[monomers]]
| 240
|-
| Monomer length (diameter)
| 70 nm
|-
| Additional envelope information
| 80 spikes; each spike is a [[trimer]] of E1/E2 proteins
|-
| Genome shape
| Linear
|-
| Genome length
| 11-12 kb
|-
| [[Nucleotide]] cap
| Yes
|-
| [[Polyadenylation|Polyadenylated]] tail
| Yes
|-
| [[Incubation period]]
| 1-6 day(s)
|}

[[Image: Alphavirus06.jpeg|thumb|This negatively-stained 1975 [[transmission electron micrograph]] ([[TEM]]) revealed the presence of a number of Venezuelan equine encephalitis (VEE) virus virions in this tissue specimen, which had been fixed using [[phosphotungstic acid]] (PTA).<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref>]]

Venezuelan equine encephalitis is contracted by the [[bite]] of an infected [[mosquito]], primarily ''Culex melanoconion'' or ''[[Aedes]]''. Venezuelan equine encephalitis virus circulates between a mosquito vector, usually ''Culex melanoconion'', and forest [[rodent]]s in Central and South America. Transmission to humans requires mosquito species capable of creating a "bridge" between infected animals and uninfected humans, such as some ''[[Aedes]]'' and other ''Culex'' species. The [[incubation period]] is 1-6 day(s).<ref name=VEECanPH2> VENEZUELAN EQUINE ENCEPHALITIS VIRUS: PATHOGEN SAFETY DATA SHEET - INFECTIOUS SUBSTANCES. Public Health Agency of Canada. (2011) http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/ven-encephalit-eng.php Accessed on March 31, 2016. </ref> In contrast to many other [[arbovirus|arboviral]] infections, infected humans possess sufficient [[viremia]] to infect uninfected mosquitos.<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref> Additionally, while a link has never been proven, there is speculation that transmission between humans is possible, as 40% of cases demonstrate infection in the [[pharynx]].<ref name="pmid956360">{{cite journal| author=Bowen GS, Calisher CH| title=Virological and serological studies of Venezuelan equine encephalomyelitis in humans. | journal=J Clin Microbiol | year= 1976 | volume= 4 | issue= 1 | pages= 22-7 | pmid=956360 | doi= | pmc=PMC274383 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=956360 }} </ref>

Venezuelan equine encephalitis virus is transmitted in the following pattern:<ref name=ViralZoneAlpha> Alphavirus. SIB Swiss Institute of Bioinformatics. http://viralzone.expasy.org/viralzone/all_by_species/625.html Accessed on March 15, 2016 </ref>

#Attachment of the viral E [[glycoprotein]] to host receptors mediates [[clathrin]] [[endocytosis]] of virus into the host cell.
#Fusion of [[biological membrane|virus membrane]] with the host [[cell membrane]]. RNA genome is released into the [[cytoplasm]].
#The [[positive-sense ssRNA virus]] is [[translate]]d into a [[polyprotein]], which is cleaved into non-structural proteins necessary for RNA synthesis ([[replication]] and [[transcription]]).
#[[Replication]] takes place in [[cytoplasm]]ic viral factories at the surface of [[endosome]]s. A [[dsRNA]] [[genome]] is synthesized from the genomic ssRNA(+).
#The [[dsRNA]] [[genome]] is [[transcribed]] thereby providing viral [[mRNA]]s (new ssRNA(+) genomes).
#Expression of the subgenomic RNA (sgRNA) gives rise to the structural proteins.
#Virus assembly occurs at the [[endoplasmic reticulum]].
#[[Virion]]s bud at the [[endoplasmic reticulum]], are transported to the [[Golgi apparatus]], and then exit the cell via the [[secretory pathway]].

On microscopic histopathological analysis, the enveloped, spherical, and [[icosahedral]] virion shape are characteristic findings of Venezuelan equine encephalitis.

==Causes==
Venezuelan equine encephalitis may be caused by Venezuelan equine encephalitis virus.

==Differentiating Venezuelan equine encephalitis from Other Diseases==
Venezuelan equine encephalitis virus must be differentiated from other diseases that cause [[fever]], [[headache]], [[seizures]], and [[altered mental status]], such as:<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref><ref name="pmid14978145">{{cite journal| author=Kennedy PG| title=Viral encephalitis: causes, differential diagnosis, and management. | journal=J Neurol Neurosurg Psychiatry | year= 2004 | volume= 75 Suppl 1 | issue= | pages= i10-5 | pmid=14978145 | doi= | pmc=PMC1765650 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14978145 }} </ref><ref name=NYDeptofHealth> Arboviral Infections (arthropod-borne encephalitis, eastern equine encephalitis, St. Louis encephalitis, California encephalitis, Powassan encephalitis, West Nile encephalitis). New York State Department of Health (2006). https://www.health.ny.gov/diseases/communicable/arboviral/fact_sheet.htm Accessed on February 23, 2016 </ref>

{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
|+
! style="background: #4479BA; width: 120px;" | {{fontcolor|#FFF|Disease}}
! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|Findings}}
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Meningitis]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Meningitis]] presents with [[headache]], [[altered mental status]], and [[inflammation]] of the [[meninges]], which may develop in the setting of an [[infection]], physical injury, [[cancer]], or certain drugs; it may have an indolent evolution, resolving on its own, or may present as an rapidly evolving [[inflammation]], causing neurologic damage and possible [[mortality]]. {{see also|Bacterial meningitis|Viral meningitis|Fungal meningitis}}
|-
| style="padding: 5px 5px; background: #DCDCDC;" |'''[[Brain abscess]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Brain abscess]] presents with an [[abscess]] in the [[brain]] caused by the [[inflammation]] and accumulation of [[infected]] material from local or remote infectious areas of the body; the infectious agent may also be introduced as a result of head [[trauma]] or [[neurosurgery|neurological procedures]].
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Acute disseminated encephalomyelitis]] (ADEM)'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Acute disseminated encephalomyelitis]] presents with scattered foci of [[demyelination]] and perivenular [[inflammation]]; it can cause focal neurological signs and decreased ability to focus.
|-
|}

==Epidemiology and Demographics==
The [[case fatality|case-fatality]] rate of Venezuelan equine encephalitis is approximately 0.7.<ref name="pmid8709783">{{cite journal| author=Weaver SC, Salas R, Rico-Hesse R, Ludwig GV, Oberste MS, Boshell J et al.| title=Re-emergence of epidemic Venezuelan equine encephalomyelitis in South America. VEE Study Group. | journal=Lancet | year= 1996 | volume= 348 | issue= 9025 | pages= 436-40 | pmid=8709783 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8709783 }} </ref>
===Age===
Patients of all age groups may develop Venezuelan equine encephalitis.<ref name="pmid9086137">{{cite journal| author=Rivas F, Diaz LA, Cardenas VM, Daza E, Bruzon L, Alcala A et al.| title=Epidemic Venezuelan equine encephalitis in La Guajira, Colombia, 1995. | journal=J Infect Dis | year= 1997 | volume= 175 | issue= 4 | pages= 828-32 | pmid=9086137 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9086137 }} </ref>

===Gender===
Venezuelan equine encephalitis affects men and women equally.<ref name="pmid9086137">{{cite journal| author=Rivas F, Diaz LA, Cardenas VM, Daza E, Bruzon L, Alcala A et al.| title=Epidemic Venezuelan equine encephalitis in La Guajira, Colombia, 1995. | journal=J Infect Dis | year= 1997 | volume= 175 | issue= 4 | pages= 828-32 | pmid=9086137 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9086137 }} </ref>

===Race===
There is no racial predilection for Venezuelan equine encephalitis.

===Seasonal===
Venezuelan equine encephalitis is most commonly observed in the summer months or after periods of heavy rainfall.

===Geographic Distribution===
The majority of Venezuelan equine encephalitis cases are reported in South America, specifically Columbia and Venezuela.

==Risk Factors==
Common [[risk factor]]s in the development of Venezuelan equine encephalitis are:
*Summer season
*Outdoor recreational activities
*Residing or visiting Central and South America
*Contact with:
**[[Mosquito]]s
**Birds
**Horses
**[[Rodent]]s
**Infected persons

==Natural History, Complications, and Prognosis==
===Natural History===
If left untreated, patients with Venezuelan equine encephalitis may progress to [[febrile]] [[prodrome]] followed by [[meningismus]], [[weakness]], [[tremor]]s, and [[altered mental status]].

===Complications===
Complications of Venezuelan equine encephalitis include:
*[[Seizure]]s
*Loss of basic [[motor skill]]s
*Loss of [[coordination]]
*[[Meningitis]]
*[[Dysarthria]]
*[[Affective disorders]]
*[[Miscarriage]] in pregnant women

===Prognosis===
Prognosis for Venezuelan equine encephalitis is generally good; less than 1% of patients infected with the Venezuelan equine encephalitis virus present with symptoms. Symptomatic patients often recover within 2-3 weeks of infection.

==Diagnosis==
===Diagnostic criteria===
Neuroinvasive vs non-neuroinvasive Venezuelan equine encephalitis can be differentiated based on both clinical and laboratory findings. These include:<ref name=CDCCritArboInvasive> Arboviral diseases, neuroinvasive and non-neuroinvasive 2015 Case Definition. National Notifiable Diseases Surveillance System (NNDSS). Centers for Disease Control (2015). https://wwwn.cdc.gov/nndss/conditions/arboviral-diseases-neuroinvasive-and-non-neuroinvasive/case-definition/2015/ Accessed on March 31, 2016. </ref>

{| class="wikitable"
! style="text-align: center; font-weight: bold;" | Venezuelan Equine Encephalitis Subtype
! style="text-align: center; font-weight: bold;" | Clinical Presentation
! style="text-align: center; font-weight: bold;" | Laboratory Findings
|-
| style="font-style: italic;" | Neuroinvasive
|
:{{unicode|☑}} [[Meningitis]], [[encephalitis]], acute flaccid [[paralysis]], or other acute signs of central or peripheral neurologic dysfunction, as documented by a [[physician]] '''AND'''
:{{unicode|☑}} Absence of a more likely clinical explanation
|
:{{unicode|☑}} Isolation of [[virus]] from, or demonstration of specific viral [[antigen]] or [[nucleic acid in]], [[tissue]], [[blood]], [[cerebrospinal fluid]] (CSF) '''OR'''
:{{unicode|☑}} Four-fold or greater change in virus-specific quantitative antibody [[titer]]s in paired sera '''OR'''
:{{unicode|☑}} Virus-specific [[IgM]] antibodies in [[serum]] with confirmatory virus-specific neutralizing antibodies in the same or a later specimen '''OR'''
:{{unicode|☑}} Virus-specific [[IgM]] antibodies in [[cerebrospinal fluid]], with or without a reported [[pleocytosis]], and a negative result for other IgM antibodies in cerebrospinal fluid for arboviruses endemic to the region where exposure occurred
|-
| style="font-style: italic;" | Non-neuroinvasive
|
:{{unicode|☑}} [[Fever]] and [[chills]] as reported by the [[patient]] or a [[health care provider]] '''AND'''
:{{unicode|☑}} Absence of [[invasive|neuroinvasive]] disease '''AND'''
:{{unicode|☑}} Absence of a more likely clinical explanation
|
:{{unicode|☑}} Isolation of [[virus]] from, or demonstration of specific viral [[antigen]] or [[nucleic acid]] in, [[tissue]], [[blood]], or other body fluid, excluding [[cerebrospinal fluid]] '''OR'''
:{{unicode|☑}} Four-fold or greater change in virus-specific quantitative antibody [[titer]]s in paired sera '''OR'''
:{{unicode|☑}} Virus-specific [[IgM]] antibodies in [[serum]] with confirmatory virus-specific neutralizing antibodies in the same or a later specimen
|}

===History and Symptoms===
If possible, a detailed and thorough history from the patient is necessary. If the patient is female, a pregnancy test should be administered to monitor for potential [[miscarriage]]. Venezuelan equine encephalitis is usually asymptomatic. Less common symptoms of Venezuelan equine encephalitis include:<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref><ref name= NINDS> Meningitis and Encephalitis Fact Sheet. National Institute of Neurological Disorders and Stroke. National Institutes of Health (2015). http://www.ninds.nih.gov/disorders/encephalitis_meningitis/detail_encephalitis_meningitis.htm Accessed on February 9, 2015 </ref>
*[[Fever]]
*[[Chills]]
*[[Headache]]
*[[Fatigue]]
*[[myalgia|Muscle pain]]
*[[Arthralgia|Joint pain]]
*[[pharyngeal|Throat pain]]
*[[Dizziness]]
*[[photophobia|Light-sensitivity]]
*[[Altered mental status]]

===Physical Examination===
Physical examination for Venezuelan equine encephalitis may be remarkable for:<ref name="pmid20551475">{{cite journal| author=Steele KE, Twenhafel NA| title=REVIEW PAPER: pathology of animal models of alphavirus encephalitis. | journal=Vet Pathol | year= 2010 | volume= 47 | issue= 5 | pages= 790-805 | pmid=20551475 | doi=10.1177/0300985810372508 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20551475 }} </ref>
*[[Fever]]
*[[Ataxia]]
*[[Seizure]]s
*[[Obtundation]]
*[[Myalgia]]
*[[myelitis|Acute flaccid myelitis]]
*[[Lethargy]]
*[[Meningism]]
*[[Photophobia]]
*[[Somnolence]]
*[[Coma]]
*[[Motor neuron]] dysfunction
*[[Tremor]]
*[[Pharyngeal]] pain
*[[Cervical]] [[lymphadenopathy]]

===Laboratory Findings===
The diagnostic method of choice for Venezuelan equine encephalitis is laboratory testing. The positive presence of [[IgM]] [[antibody|antibodies]] is diagnostic of Venezuelan equine encephalitis. Other laboratory findings consistent with the diagnosis of Venezuelan equine encephalitis include:<ref name=IDSAEnceph> The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America. http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Encephalitis.pdf Accessed on February 16, 2016.</ref>
*[[Serologic]] [[cross-reactivity]]
*Persistence of [[IgG]] and neutralizing [[antibody|antibodies]]
*Confirmation of arboviral-specific neutralizing antibodies in [[enzyme linked immunosorbent assay (ELISA)]] or [[polymerase chain reaction|polymerase chain reaction (PCR)]]
*In [[cerebrospinal fluid]]:
**[[Pleocytosis]]
**Increased protein levels
**Normal to slightly elevated [[glucose]] levels

===Imaging Findings===
[[MRI]] is the imaging modality of choice for Venezuelan equine encephalitis. Findings of Venezuelan equine encephalitis on MRI include T2 hyperintensity and restricted diffusion in the [[basal ganglia]] and [[thalamus]].<ref name=EncephGeneralMRI> Flavivirus encephalitis. Radiopaedia.org (2016). http://radiopaedia.org/articles/flavivirus-encephalitis Accessed on March 29, 2016. </ref> [[CT scan]] appears normal. [[EEG]] typically demonstrates diffuse slowing; some cases present with focal [[temporal]] slowing, resembling [[herpes simplex encephalitis]].

==Treatment==
===Medical Therapy===
There is no treatment for Venezuelan equine encephalitis; the mainstay of therapy is supportive care. Because supportive care is the only treatment for Venezuelan equine encephalitis, physicians often do not request the tests required to specifically identify the Venezuelan equine encephalitis virus.

===Surgery===
Surgical intervention is not recommended for the management of Venezuelan equine encephalitis.

===Prevention===
TC-83 is is a live, [[attenuated]] [[vaccine]] recommended for at risk military and [[laboratory]] personnel to prevent Venezuelan equine encephalitis. Mild to moderate [[adverse drug reaction|adverse reactions]] have been noted in up to 25% of patients.<ref name="pmid19837294">{{cite journal| author=Paessler S, Weaver SC| title=Vaccines for Venezuelan equine encephalitis. | journal=Vaccine | year= 2009 | volume= 27 Suppl 4 | issue= | pages= D80-5 | pmid=19837294 | doi=10.1016/j.vaccine.2009.07.095 | pmc=PMC2764542 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19837294 }} </ref> In some cases, the TC-83 strain does not provide sufficient [[immunization]] and may be bolstered with a C-84 vaccine. The vaccine has not been proven as fully effective against [[aerosol]] exposure.<ref name=MicroBioVEEV> Venezuelan equine encephalitis virus. MicrobeWiki (2010) https://microbewiki.kenyon.edu/index.php/Venezuelan_equine_encephalitis_virus Accessed on April 5, 2016. </ref> Currently only the C-84 vaccine is licensed for use in horses in the United States, although countries, such as Mexico and Colombia, still produce the live vaccine for horses.

Other primary prevention strategies for Venezuelan equine encephalitis include:<ref name=EEENYPubHealth> Eastern Equine Encephalitis (EEE). New York State Department of Public Health (2012). https://www.health.ny.gov/diseases/communicable/eastern_equine_encephalitis/fact_sheet.htm Accessed on March 15, 2016.</ref>
*Removal of [[standing water]]
*Screens on doors and windows
*When outdoors, wearing:
**Insect repellent containing [[DEET]]
**Long sleeves, pants; tucking in pants into high socks

==References==
{{Reflist|2}}

[[Category:Viruses]]
[[Category:Neurology]]
[[Category:Infectious disease]]

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Venezuelan equine encephalitis

2016-04-20T15:02:37Z

Sergekorjian:

__NOTOC__
{{SI}}
{{CMG}} {{AE}} {{AG}}

{{SK}} VEE; VEEV; Venezuelan equine encephalitis virus; Venezuelan encephalitis; Venezuelan equine encephalomyelitis; Venezuelan equine fever

==Overview==
Venezuelan equine encephalitis is a mild to moderate, though sometimes [[fatal]], infection of the [[central nervous system]]. Venezuelan equine encephalitis belongs to the Group IV positive-sense ssRNA virus within the ''[[Togaviridae]]'' family of viruses, and the genus ''[[Alphavirus]]''. Venezuelan equine encephalitis virus is usually transmitted via [[mosquito]]s to the human host, primarily ''Culex melanoconion'' or ''[[Aedes]]''. Venezuelan equine encephalitis virus must be differentiated from other diseases that cause [[fever]], [[headache]], [[seizures]], and [[altered mental status]]. Prognosis for Venezuelan equine encephalitis is generally good; less than 1% of patients infected with the Venezuelan equine encephalitis virus present with symptoms. Symptomatic patients often recover within 2-3 weeks of infection. The [[case fatality|case-fatality]] rate of Venezuelan equine encephalitis is approximately 0.7. If possible, a detailed and thorough history from the patient is necessary. If the patient is female, a pregnancy test should be administered to monitor for potential [[miscarriage]]. Venezuelan equine encephalitis is usually asymptomatic. The diagnostic method of choice for Venezuelan equine encephalitis is laboratory testing. There is no treatment for Venezuelan equine encephalitis; the mainstay of therapy is supportive care. There is a vaccination approved for limited use for Venezuelan equine encephalitis, though its effectiveness is often questioned.

==Historical Perspective==
Venezuelan equine encephalitis was first discovered in 1938 after the virus was isolated from the [[brain]]s of dead horses following an outbreak in the Venezuelan countryside.<ref name="pmid17840536">{{cite journal| author=Beck CE, Wyckoff RW| title=VENEZUELAN EQUINE ENCEPHALOMYELITIS. | journal=Science | year= 1938 | volume= 88 | issue= 2292 | pages= 530 | pmid=17840536 | doi=10.1126/science.88.2292.530 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17840536 }} </ref> There have been several outbreaks of Venezuelan equine encephalitis. In 1995, the last major [[outbreak]] occurred in Venezuela and Columbia and resulted in approximately 75,000 cases, of which 3,000 had severe [[neurological]] [[complication]]s and 300 progressed to [[mortality]].<ref name="pmid9086137">{{cite journal| author=Rivas F, Diaz LA, Cardenas VM, Daza E, Bruzon L, Alcala A et al.| title=Epidemic Venezuelan equine encephalitis in La Guajira, Colombia, 1995. | journal=J Infect Dis | year= 1997 | volume= 175 | issue= 4 | pages= 828-32 | pmid=9086137 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9086137 }} </ref> The last reported case of Venezuelan equine encephalitis in the United States occurred in southern Texas in 1972.<ref name=VEEVCanPH1> Venezuelan Equine Encephalomyelitis - Fact Sheet. Canadian Food Inspection Agency (2012). http://www.inspection.gc.ca/animals/terrestrial-animals/diseases/reportable/venezuelan-equine-encephalomyelitis/fact-sheet/eng/1329841926239/1329842048136 Accessed on March 31, 2016. </ref>

==Classification==
Venezuelan equine encephalitis may be classified according to location of the disease into 2 subtypes: systemic or encephalitic. Venezuelan equine encephalitis may also be classified according to [[invasive|neuroinvasiveness]] of the disease into 2 subtypes: neuroinvasive and non-neuroinvasive.<ref name=CDCCritArboInvasive> Arboviral diseases, neuroinvasive and non-neuroinvasive 2015 Case Definition. National Notifiable Diseases Surveillance System (NNDSS). Centers for Disease Control (2015). https://wwwn.cdc.gov/nndss/conditions/arboviral-diseases-neuroinvasive-and-non-neuroinvasive/case-definition/2015/ Accessed on March 31, 2016. </ref> Venezuelan equine encephalitis belongs to the Group IV positive-sense ssRNA virus within the ''[[Togaviridae]]'' family of viruses, and the genus ''[[Alphavirus]]''. Venezuelan equine encephalitis is closely related to [[eastern equine encephalitis]] virus and [[western equine encephalitis]] virus. Venezuelan equine encephalitis is known as an [[arbovirus]], or an arthropod-borne virus.

==Pathophysiology==
Venezuelan equine encephalitis virus is usually transmitted via [[mosquito]]s to the human host. Venezuelan equine encephalitis virus contains [[positive-sense ssRNA virus|positive-sense]] viral [[RNA]]; this RNA has its genome directly utilized as if it were mRNA, producing a single protein which is modified by host and viral proteins to form the various proteins needed for [[replication]]. The following table is a summary of the Venezuelan equine encephalitis virus:<ref name=ViralZoneAlpha> Alphavirus. SIB Swiss Institute of Bioinformatics. http://viralzone.expasy.org/viralzone/all_by_species/625.html Accessed on March 15, 2016 </ref>

{| class="wikitable"
! style="text-align: center; font-weight: bold;" | Characteristic
! style="text-align: center; font-weight: bold;" | Data
|-
| Nucleic acid
| [[RNA]]
|-
| Sense
| [[positive-sense ssRNA virus|ssRNA(+)]]
|-
| Virion
| [[enveloped virus|Enveloped]]
|-
| [[Capsid]]
| Spherical
|-
| Symmetry
| Yes; T=4 [[icosahedral]]
|-
| Capsid [[monomers]]
| 240
|-
| Monomer length (diameter)
| 70 nm
|-
| Additional envelope information
| 80 spikes; each spike is a [[trimer]] of E1/E2 proteins
|-
| Genome shape
| Linear
|-
| Genome length
| 11-12 kb
|-
| [[Nucleotide]] cap
| Yes
|-
| [[Polyadenylation|Polyadenylated]] tail
| Yes
|-
| [[Incubation period]]
| 1-6 day(s)
|}

[[Image: Alphavirus06.jpeg|thumb|This negatively-stained 1975 [[transmission electron micrograph]] ([[TEM]]) revealed the presence of a number of Venezuelan equine encephalitis (VEE) virus virions in this tissue specimen, which had been fixed using [[phosphotungstic acid]] (PTA).<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref>]]

Venezuelan equine encephalitis is contracted by the [[bite]] of an infected [[mosquito]], primarily ''Culex melanoconion'' or ''[[Aedes]]''. Venezuelan equine encephalitis virus circulates between a mosquito vector, usually ''Culex melanoconion'', and forest [[rodent]]s in Central and South America. Transmission to humans requires mosquito species capable of creating a "bridge" between infected animals and uninfected humans, such as some ''[[Aedes]]'' and other ''Culex'' species. The [[incubation period]] is 1-6 day(s).<ref name=VEECanPH2> VENEZUELAN EQUINE ENCEPHALITIS VIRUS: PATHOGEN SAFETY DATA SHEET - INFECTIOUS SUBSTANCES. Public Health Agency of Canada. (2011) http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/ven-encephalit-eng.php Accessed on March 31, 2016. </ref> In contrast to many other [[arbovirus|arboviral]] infections, infected humans possess sufficient [[viremia]] to infect uninfected mosquitos.<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref> Additionally, while a link has never been proven, there is speculation that transmission between humans is possible, as 40% of cases demonstrate infection in the [[pharynx]].<ref name="pmid956360">{{cite journal| author=Bowen GS, Calisher CH| title=Virological and serological studies of Venezuelan equine encephalomyelitis in humans. | journal=J Clin Microbiol | year= 1976 | volume= 4 | issue= 1 | pages= 22-7 | pmid=956360 | doi= | pmc=PMC274383 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=956360 }} </ref>

Venezuelan equine encephalitis virus is transmitted in the following pattern:<ref name=ViralZoneAlpha> Alphavirus. SIB Swiss Institute of Bioinformatics. http://viralzone.expasy.org/viralzone/all_by_species/625.html Accessed on March 15, 2016 </ref>

#Attachment of the viral E [[glycoprotein]] to host receptors mediates [[clathrin]] [[endocytosis]] of virus into the host cell.
#Fusion of [[biological membrane|virus membrane]] with the host [[cell membrane]]. RNA genome is released into the [[cytoplasm]].
#The [[positive-sense ssRNA virus]] is [[translate]]d into a [[polyprotein]], which is cleaved into non-structural proteins necessary for RNA synthesis ([[replication]] and [[transcription]]).
#[[Replication]] takes place in [[cytoplasm]]ic viral factories at the surface of [[endosome]]s. A [[dsRNA]] [[genome]] is synthesized from the genomic ssRNA(+).
#The [[dsRNA]] [[genome]] is [[transcribed]] thereby providing viral [[mRNA]]s (new ssRNA(+) genomes).
#Expression of the subgenomic RNA (sgRNA) gives rise to the structural proteins.
#Virus assembly occurs at the [[endoplasmic reticulum]].
#[[Virion]]s bud at the [[endoplasmic reticulum]], are transported to the [[Golgi apparatus]], and then exit the cell via the [[secretory pathway]].

On microscopic histopathological analysis, the enveloped, spherical, and [[icosahedral]] virion shape are characteristic findings of Venezuelan equine encephalitis.

==Causes==
Venezuelan equine encephalitis may be caused by Venezuelan equine encephalitis virus.

==Differentiating Venezuelan equine encephalitis from Other Diseases==
Venezuelan equine encephalitis virus must be differentiated from other diseases that cause [[fever]], [[headache]], [[seizures]], and [[altered mental status]], such as:<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref><ref name="pmid14978145">{{cite journal| author=Kennedy PG| title=Viral encephalitis: causes, differential diagnosis, and management. | journal=J Neurol Neurosurg Psychiatry | year= 2004 | volume= 75 Suppl 1 | issue= | pages= i10-5 | pmid=14978145 | doi= | pmc=PMC1765650 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14978145 }} </ref><ref name=NYDeptofHealth> Arboviral Infections (arthropod-borne encephalitis, eastern equine encephalitis, St. Louis encephalitis, California encephalitis, Powassan encephalitis, West Nile encephalitis). New York State Department of Health (2006). https://www.health.ny.gov/diseases/communicable/arboviral/fact_sheet.htm Accessed on February 23, 2016 </ref>

{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
|+
! style="background: #4479BA; width: 120px;" | {{fontcolor|#FFF|Disease}}
! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|Findings}}
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Eastern equine encephalitis]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Eastern equine encephalitis]] presents with acute [[inflammation]] of the [[brain]], caused by an [[arbovirus|arboviral infection]]; Venezuelan equine encephalitis is less severe than Eastern equine encephalitis. Other findings include [[fever]], [[nausea]], [[headache]], [[vomit]]ing, [[photophobia]], [[seizure]]s, and [[coma]].
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Western equine encephalitis]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Western equine encephalitis]] presents with acute [[inflammation]] of the [[brain]], caused by an [[arbovirus|arboviral infection]]; Venezuelan equine encephalitis is less severe than Western equine encephalitis. Other findings include [[fever]], [[nausea]], [[headache]], [[vomit]]ing, [[photophobia]], [[seizure]]s, and [[coma]].
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Vector-borne encephalitis]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Vector-borne encephalitis]] presents with acute [[inflammation]] of the [[brain]], caused by a [[bacterial infection]]; complications include severe [[brain]] damage as the inflamed [[brain]] pushes against the [[skull]], potentially leading to [[mortality]]. {{see also|Tick-borne encephalitis|California encephalitis virus|La Crosse encephalitis|Japanese encephalitis|West Nile encephalitis}}
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Viral encephalitis]] '''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Viral encephalitis]] presents with acute [[inflammation]] of the [[brain]], caused by a [[viral infection]]; complications include severe [[brain]] damage as the inflamed [[brain]] pushes against the [[skull]], potentially leading to [[mortality]]. {{see also|Herpes simplex encephalitis|VZV encephalitis}}
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Encephalopathy]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Encephalopathy]] presents with steady [[depression]], generalized [[seizures]]. Generally absent are [[fever]], [[headache]], [[leukocytosis]], and [[pleocytosis]]; [[MRI]] often appears normal.
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Meningitis]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Meningitis]] presents with [[headache]], [[altered mental status]], and [[inflammation]] of the [[meninges]], which may develop in the setting of an [[infection]], physical injury, [[cancer]], or certain drugs; it may have an indolent evolution, resolving on its own, or may present as an rapidly evolving [[inflammation]], causing neurologic damage and possible [[mortality]]. {{see also|Bacterial meningitis|Viral meningitis|Fungal meningitis}}
|-
| style="padding: 5px 5px; background: #DCDCDC;" |'''[[Brain abscess]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Brain abscess]] presents with an [[abscess]] in the [[brain]] caused by the [[inflammation]] and accumulation of [[infected]] material from local or remote infectious areas of the body; the infectious agent may also be introduced as a result of head [[trauma]] or [[neurosurgery|neurological procedures]].
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Acute disseminated encephalomyelitis]] (ADEM)'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Acute disseminated encephalomyelitis]] presents with scattered foci of [[demyelination]] and perivenular [[inflammation]]; it can cause focal neurological signs and decreased ability to focus.
|-
|}

==Epidemiology and Demographics==
The [[case fatality|case-fatality]] rate of Venezuelan equine encephalitis is approximately 0.7.<ref name="pmid8709783">{{cite journal| author=Weaver SC, Salas R, Rico-Hesse R, Ludwig GV, Oberste MS, Boshell J et al.| title=Re-emergence of epidemic Venezuelan equine encephalomyelitis in South America. VEE Study Group. | journal=Lancet | year= 1996 | volume= 348 | issue= 9025 | pages= 436-40 | pmid=8709783 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8709783 }} </ref>
===Age===
Patients of all age groups may develop Venezuelan equine encephalitis.<ref name="pmid9086137">{{cite journal| author=Rivas F, Diaz LA, Cardenas VM, Daza E, Bruzon L, Alcala A et al.| title=Epidemic Venezuelan equine encephalitis in La Guajira, Colombia, 1995. | journal=J Infect Dis | year= 1997 | volume= 175 | issue= 4 | pages= 828-32 | pmid=9086137 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9086137 }} </ref>

===Gender===
Venezuelan equine encephalitis affects men and women equally.<ref name="pmid9086137">{{cite journal| author=Rivas F, Diaz LA, Cardenas VM, Daza E, Bruzon L, Alcala A et al.| title=Epidemic Venezuelan equine encephalitis in La Guajira, Colombia, 1995. | journal=J Infect Dis | year= 1997 | volume= 175 | issue= 4 | pages= 828-32 | pmid=9086137 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9086137 }} </ref>

===Race===
There is no racial predilection for Venezuelan equine encephalitis.

===Seasonal===
Venezuelan equine encephalitis is most commonly observed in the summer months or after periods of heavy rainfall.

===Geographic Distribution===
The majority of Venezuelan equine encephalitis cases are reported in South America, specifically Columbia and Venezuela.

==Risk Factors==
Common [[risk factor]]s in the development of Venezuelan equine encephalitis are:
*Summer season
*Outdoor recreational activities
*Residing or visiting Central and South America
*Contact with:
**[[Mosquito]]s
**Birds
**Horses
**[[Rodent]]s
**Infected persons

==Natural History, Complications, and Prognosis==
===Natural History===
If left untreated, patients with Venezuelan equine encephalitis may progress to [[febrile]] [[prodrome]] followed by [[meningismus]], [[weakness]], [[tremor]]s, and [[altered mental status]].

===Complications===
Complications of Venezuelan equine encephalitis include:
*[[Seizure]]s
*Loss of basic [[motor skill]]s
*Loss of [[coordination]]
*[[Meningitis]]
*[[Dysarthria]]
*[[Affective disorders]]
*[[Miscarriage]] in pregnant women

===Prognosis===
Prognosis for Venezuelan equine encephalitis is generally good; less than 1% of patients infected with the Venezuelan equine encephalitis virus present with symptoms. Symptomatic patients often recover within 2-3 weeks of infection.

==Diagnosis==
===Diagnostic criteria===
Neuroinvasive vs non-neuroinvasive Venezuelan equine encephalitis can be differentiated based on both clinical and laboratory findings. These include:<ref name=CDCCritArboInvasive> Arboviral diseases, neuroinvasive and non-neuroinvasive 2015 Case Definition. National Notifiable Diseases Surveillance System (NNDSS). Centers for Disease Control (2015). https://wwwn.cdc.gov/nndss/conditions/arboviral-diseases-neuroinvasive-and-non-neuroinvasive/case-definition/2015/ Accessed on March 31, 2016. </ref>

{| class="wikitable"
! style="text-align: center; font-weight: bold;" | Venezuelan Equine Encephalitis Subtype
! style="text-align: center; font-weight: bold;" | Clinical Presentation
! style="text-align: center; font-weight: bold;" | Laboratory Findings
|-
| style="font-style: italic;" | Neuroinvasive
|
:{{unicode|☑}} [[Meningitis]], [[encephalitis]], acute flaccid [[paralysis]], or other acute signs of central or peripheral neurologic dysfunction, as documented by a [[physician]] '''AND'''
:{{unicode|☑}} Absence of a more likely clinical explanation
|
:{{unicode|☑}} Isolation of [[virus]] from, or demonstration of specific viral [[antigen]] or [[nucleic acid in]], [[tissue]], [[blood]], [[cerebrospinal fluid]] (CSF) '''OR'''
:{{unicode|☑}} Four-fold or greater change in virus-specific quantitative antibody [[titer]]s in paired sera '''OR'''
:{{unicode|☑}} Virus-specific [[IgM]] antibodies in [[serum]] with confirmatory virus-specific neutralizing antibodies in the same or a later specimen '''OR'''
:{{unicode|☑}} Virus-specific [[IgM]] antibodies in [[cerebrospinal fluid]], with or without a reported [[pleocytosis]], and a negative result for other IgM antibodies in cerebrospinal fluid for arboviruses endemic to the region where exposure occurred
|-
| style="font-style: italic;" | Non-neuroinvasive
|
:{{unicode|☑}} [[Fever]] and [[chills]] as reported by the [[patient]] or a [[health care provider]] '''AND'''
:{{unicode|☑}} Absence of [[invasive|neuroinvasive]] disease '''AND'''
:{{unicode|☑}} Absence of a more likely clinical explanation
|
:{{unicode|☑}} Isolation of [[virus]] from, or demonstration of specific viral [[antigen]] or [[nucleic acid]] in, [[tissue]], [[blood]], or other body fluid, excluding [[cerebrospinal fluid]] '''OR'''
:{{unicode|☑}} Four-fold or greater change in virus-specific quantitative antibody [[titer]]s in paired sera '''OR'''
:{{unicode|☑}} Virus-specific [[IgM]] antibodies in [[serum]] with confirmatory virus-specific neutralizing antibodies in the same or a later specimen
|}

===History and Symptoms===
If possible, a detailed and thorough history from the patient is necessary. If the patient is female, a pregnancy test should be administered to monitor for potential [[miscarriage]]. Venezuelan equine encephalitis is usually asymptomatic. Less common symptoms of Venezuelan equine encephalitis include:<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref><ref name= NINDS> Meningitis and Encephalitis Fact Sheet. National Institute of Neurological Disorders and Stroke. National Institutes of Health (2015). http://www.ninds.nih.gov/disorders/encephalitis_meningitis/detail_encephalitis_meningitis.htm Accessed on February 9, 2015 </ref>
*[[Fever]]
*[[Chills]]
*[[Headache]]
*[[Fatigue]]
*[[myalgia|Muscle pain]]
*[[Arthralgia|Joint pain]]
*[[pharyngeal|Throat pain]]
*[[Dizziness]]
*[[photophobia|Light-sensitivity]]
*[[Altered mental status]]

===Physical Examination===
Physical examination for Venezuelan equine encephalitis may be remarkable for:<ref name="pmid20551475">{{cite journal| author=Steele KE, Twenhafel NA| title=REVIEW PAPER: pathology of animal models of alphavirus encephalitis. | journal=Vet Pathol | year= 2010 | volume= 47 | issue= 5 | pages= 790-805 | pmid=20551475 | doi=10.1177/0300985810372508 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20551475 }} </ref>
*[[Fever]]
*[[Ataxia]]
*[[Seizure]]s
*[[Obtundation]]
*[[Myalgia]]
*[[myelitis|Acute flaccid myelitis]]
*[[Lethargy]]
*[[Meningism]]
*[[Photophobia]]
*[[Somnolence]]
*[[Coma]]
*[[Motor neuron]] dysfunction
*[[Tremor]]
*[[Pharyngeal]] pain
*[[Cervical]] [[lymphadenopathy]]

===Laboratory Findings===
The diagnostic method of choice for Venezuelan equine encephalitis is laboratory testing. The positive presence of [[IgM]] [[antibody|antibodies]] is diagnostic of Venezuelan equine encephalitis. Other laboratory findings consistent with the diagnosis of Venezuelan equine encephalitis include:<ref name=IDSAEnceph> The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America. http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Encephalitis.pdf Accessed on February 16, 2016.</ref>
*[[Serologic]] [[cross-reactivity]]
*Persistence of [[IgG]] and neutralizing [[antibody|antibodies]]
*Confirmation of arboviral-specific neutralizing antibodies in [[enzyme linked immunosorbent assay (ELISA)]] or [[polymerase chain reaction|polymerase chain reaction (PCR)]]
*In [[cerebrospinal fluid]]:
**[[Pleocytosis]]
**Increased protein levels
**Normal to slightly elevated [[glucose]] levels

===Imaging Findings===
[[MRI]] is the imaging modality of choice for Venezuelan equine encephalitis. Findings of Venezuelan equine encephalitis on MRI include T2 hyperintensity and restricted diffusion in the [[basal ganglia]] and [[thalamus]].<ref name=EncephGeneralMRI> Flavivirus encephalitis. Radiopaedia.org (2016). http://radiopaedia.org/articles/flavivirus-encephalitis Accessed on March 29, 2016. </ref> [[CT scan]] appears normal. [[EEG]] typically demonstrates diffuse slowing; some cases present with focal [[temporal]] slowing, resembling [[herpes simplex encephalitis]].

==Treatment==
===Medical Therapy===
There is no treatment for Venezuelan equine encephalitis; the mainstay of therapy is supportive care. Because supportive care is the only treatment for Venezuelan equine encephalitis, physicians often do not request the tests required to specifically identify the Venezuelan equine encephalitis virus.

===Surgery===
Surgical intervention is not recommended for the management of Venezuelan equine encephalitis.

===Prevention===
TC-83 is is a live, [[attenuated]] [[vaccine]] recommended for at risk military and [[laboratory]] personnel to prevent Venezuelan equine encephalitis. Mild to moderate [[adverse drug reaction|adverse reactions]] have been noted in up to 25% of patients.<ref name="pmid19837294">{{cite journal| author=Paessler S, Weaver SC| title=Vaccines for Venezuelan equine encephalitis. | journal=Vaccine | year= 2009 | volume= 27 Suppl 4 | issue= | pages= D80-5 | pmid=19837294 | doi=10.1016/j.vaccine.2009.07.095 | pmc=PMC2764542 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19837294 }} </ref> In some cases, the TC-83 strain does not provide sufficient [[immunization]] and may be bolstered with a C-84 vaccine. The vaccine has not been proven as fully effective against [[aerosol]] exposure.<ref name=MicroBioVEEV> Venezuelan equine encephalitis virus. MicrobeWiki (2010) https://microbewiki.kenyon.edu/index.php/Venezuelan_equine_encephalitis_virus Accessed on April 5, 2016. </ref> Currently only the C-84 vaccine is licensed for use in horses in the United States, although countries, such as Mexico and Colombia, still produce the live vaccine for horses.

Other primary prevention strategies for Venezuelan equine encephalitis include:<ref name=EEENYPubHealth> Eastern Equine Encephalitis (EEE). New York State Department of Public Health (2012). https://www.health.ny.gov/diseases/communicable/eastern_equine_encephalitis/fact_sheet.htm Accessed on March 15, 2016.</ref>
*Removal of [[standing water]]
*Screens on doors and windows
*When outdoors, wearing:
**Insect repellent containing [[DEET]]
**Long sleeves, pants; tucking in pants into high socks

==References==
{{Reflist|2}}

[[Category:Viruses]]
[[Category:Neurology]]
[[Category:Infectious disease]]

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VZV encephalitis

2016-04-20T15:01:56Z

Sergekorjian: /* Differentiating VZV Encephalitis from Other Diseases */

__NOTOC__
{{CMG}} {{AE}} {{AG}}

{{SK}} Varicella zoster virus encephalitis; Herpes zoster encephalitis; Varicella zoster encephalitis; Varicella encephalitis;

==Overview==
VZV encephalitis is a viral infection of the [[central nervous system]]. Based on the duration of symptoms, VZV encephalitis may be classified into either acute or chronic. The exact pathogenesis of VZV encephalitis is not fully understood. The [[immune system]] eliminates the virus from most locations upon initial infection, but it remains [[viral latency|latent]] in the [[dorsal root ganglion]] and the [[trigeminal]] ganglion near the base of the [[skull]]. VZV encephalitis may be caused by either varicella ([[chickenpox]]) or herpes zoster ([[shingles]]). VZV encephalitis must be differentiated from other diseases that cause [[fever]], [[headache]], [[vomiting]], and [[altered mental status]]. The incidence of VZV encephalitis is approximately 10 per 100,000 individuals affected with [[varicella]], most often [[neonates]] and the [[elderly]].<ref name="pmid7658062">{{cite journal| author=Choo PW, Donahue JG, Manson JE, Platt R| title=The epidemiology of varicella and its complications. | journal=J Infect Dis | year= 1995 | volume= 172 | issue= 3 | pages= 706-12 | pmid=7658062 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7658062 }} </ref> If left untreated, [[immunocompromised]] patients with VZV encephalitis may progress to [[mortality]]. Common complications include [[shock]], [[hypoxemia]], and [[meningitis]]. Signs of VZV encephalitis include [[fever]], [[headache]], [[ataxia]], and [[aphasia]]. Laboratory findings consistent with the diagnosis of VZV encephalitis include [[leukocytosis]] and [[pleocytosis]].<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref> [[Magnetic resonance imaging]] is the imaging modality of choice for VZV encephalitis. [[Acyclovir]] is the drug of choice to treat VZV encephalitis.

==Classification==
Based on the duration of symptoms, VZV encephalitis may be classified into either acute or chronic.

==Pathophysiology==
The exact pathogenesis of VZV encephalitis is not fully understood. It is known that VZV encephalitis is the result of the [[varicella zoster virus]], a double-stranded [[DNA virus]] within the [[Herpesviridae]] family of viruses.<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref> The [[immune system]] eliminates the virus from most locations upon initial infection, but it remains [[viral latency|latent]] in the [[dorsal root ganglion]] and the [[trigeminal]] ganglion near the base of the [[skull]]. Initial infection by VZV presents as [[chickenpox]], often in children between the ages of 1-9. VZV reactivation, which presents as [[shingles]] in adults, is the result of a decline in the frequency of VZV-specific [[T cell]]s.<ref name="pmid9300702">{{cite journal| author=Sadzot-Delvaux C, Kinchington PR, Debrus S, Rentier B, Arvin AM| title=Recognition of the latency-associated immediate early protein IE63 of varicella-zoster virus by human memory T lymphocytes. | journal=J Immunol | year= 1997 | volume= 159 | issue= 6 | pages= 2802-6 | pmid=9300702 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9300702 }} </ref> The molecular basis of reactivation remains unknown.<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref> Some histopathologic studies suggest of a postinfectious [[demyelinating]] process, while other findings cite direct viral cytopathology.<ref name="pmid6326714">{{cite journal| author=Bauman ML, Bergman I| title=Postvaricella encephalitis. | journal=Arch Neurol | year= 1984 | volume= 41 | issue= 5 | pages= 556-8 | pmid=6326714 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6326714 }} </ref><ref name="pmid4311227">{{cite journal| author=McCormick WF, Rodnitzky RL, Schochet SS, McKee AP| title=Varicella-Zoster encephalomyelitis. A morphologic and virologic study. | journal=Arch Neurol | year= 1969 | volume= 21 | issue= 6 | pages= 559-70 | pmid=4311227 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4311227 }} </ref><ref name="pmid582251">{{cite journal| author=Takashima S, Becker LE| title=Neuropathology of fatal varicella. | journal=Arch Pathol Lab Med | year= 1979 | volume= 103 | issue= 5 | pages= 209-13 | pmid=582251 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=582251 }} </ref>

==Causes==
VZV encephalitis may be caused by either varicella ([[chickenpox]]) or herpes zoster ([[shingles]]).

==Differentiating VZV Encephalitis from Other Diseases==
VZV encephalitis must be differentiated from other diseases that cause [[fever]], [[headache]], [[vomiting]], and [[altered mental status]], such as:<ref name="pmid14978145">{{cite journal| author=Kennedy PG| title=Viral encephalitis: causes, differential diagnosis, and management. | journal=J Neurol Neurosurg Psychiatry | year= 2004 | volume= 75 Suppl 1 | issue= | pages= i10-5 | pmid=14978145 | doi= | pmc=PMC1765650 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14978145 }} </ref><ref name="pmid12353193">{{cite journal| author=Gnann JW| title=Varicella-zoster virus: atypical presentations and unusual complications. | journal=J Infect Dis | year= 2002 | volume= 186 Suppl 1 | issue= | pages= S91-8 | pmid=12353193 | doi=10.1086/342963 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12353193 }} </ref><ref name="pmid13065322">{{cite journal| author=APPELBAUM E, RACHELSON MH, DOLGOPOL VB| title=Varicella encephalitis. | journal=Am J Med | year= 1953 | volume= 15 | issue= 2 | pages= 223-30 | pmid=13065322 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13065322 }} </ref>

{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
|+
! style="background: #4479BA; width: 120px;" | {{fontcolor|#FFF|Disease}}
! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|Findings}}
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Meningitis]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Meningitis]] presents with [[headache]], [[altered mental status]], and [[inflammation]] of the [[meninges]]. It may have an indolent evolution, resolving on its own, or may present as an rapidly evolving [[inflammation]], causing neurologic damage and possible [[mortality]]. {{see also|Bacterial meningitis|Viral meningitis|Fungal meningitis}}
|-
| style="padding: 5px 5px; background: #DCDCDC;" |'''[[Brain abscess]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Brain abscess]] presents with an [[abscess]] in the [[brain]] caused by the [[inflammation]] and accumulation of [[infected]] material from local or remote infectious areas of the body; the infectious agent may also be introduced as a result of head [[trauma]] or [[neurosurgery|neurological procedures]].
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Acute disseminated encephalomyelitis]] (ADEM)'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Acute disseminated encephalomyelitis]] presents with scattered foci of [[demyelination]] and perivenular [[inflammation]]; it can cause focal neurological signs and decreased ability to focus.
|-
|}

==Epidemiology and Demographics==
===Incidence===
The incidence of VZV encephalitis is approximately 10 per 100,000 individuals affected with [[varicella]].<ref name="pmid7658062">{{cite journal| author=Choo PW, Donahue JG, Manson JE, Platt R| title=The epidemiology of varicella and its complications. | journal=J Infect Dis | year= 1995 | volume= 172 | issue= 3 | pages= 706-12 | pmid=7658062 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7658062 }} </ref>

===Age===
VZV encephalitis most commonly affects infants or the [[elderly]].<ref name="pmid7658062">{{cite journal| author=Choo PW, Donahue JG, Manson JE, Platt R| title=The epidemiology of varicella and its complications. | journal=J Infect Dis | year= 1995 | volume= 172 | issue= 3 | pages= 706-12 | pmid=7658062 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7658062 }} </ref>

===Gender===
Men and women are affected equally by VZV encephalitis.

==Risk Factors==
Common risk factors in the development of VZV encephalitis include:<ref name="pmid12353193">{{cite journal| author=Gnann JW| title=Varicella-zoster virus: atypical presentations and unusual complications. | journal=J Infect Dis | year= 2002 | volume= 186 Suppl 1 | issue= | pages= S91-8 | pmid=12353193 | doi=10.1086/342963 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12353193 }} </ref><ref name="Mounsey">{{cite journal|title=Herpes zoster and postherpetic neuralgia: prevention and management|author=Mounsey AL, Matthew LG, & Slawson DC|date=2005|journal=American Family Physician|volume=72|issue=6|pages=1075-1080|pmid=16190505|url=http://www.aafp.org/afp/20050915/1075.html|accessdate=2007-06-15}}</ref><ref>{[cite journal|title=What does epidemiology tell us about risk factors for herpes zoster?|author=Thomas SL, Hall AJ|journal= Lancet Infect Dis.|date=2004|volume=4|issue=1|pages=26-33|pmid= 14720565}}</ref><ref name=IDSAEnceph> The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America. http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Encephalitis.pdf Accessed on February 16, 2016.</ref>
*[[Varicella zoster virus]] infection
*[[Immunosuppression]]
*[[HIV]] or [[AIDS]]
*[[Age]] extremes
*[[Stress]]
*Chronic [[corticosteroid]] usage
*[[Skin]] [[inflammation]]
*[[Pregnancy]]
*Living in tropical climate
*Working as a [[physician]] or other [[health care provider]]
*Absence of [[varicella vaccine]]

==Natural History, Complications, and Prognosis==
===Natural History===
Herpes zoster usually clears in 2 to 3 weeks and rarely recurs. However, if left untreated, [[immunocompromised]] patients with VZV encephalitis may progress to [[mortality]].

===Complications===
Common complications of VZV encephalitis include:<ref name="pmid14978145">{{cite journal| author=Kennedy PG| title=Viral encephalitis: causes, differential diagnosis, and management. | journal=J Neurol Neurosurg Psychiatry | year= 2004 | volume= 75 Suppl 1 | issue= | pages= i10-5 | pmid=14978145 | doi= | pmc=PMC1765650 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14978145 }} </ref>
*[[Shock]]
*[[Hypoxemia]]
*[[Hypotension]]
*[[Aphasia]]
*[[Seizures]]
*[[Meningitis]]
*Loss of [[motor skill]]s
*[[Coma]]
*[[Mortality]]

===Prognosis===
Prognosis for VZV encephalitis is generally good in most individuals. Prognosis for VZV encephalitis is poor in [[immunocompromised]] individuals.

==Diagnosis==
===History and Symptoms===
If possible, a detailed and thorough history from the patient is necessary. Symptoms of VZV encephalitis include:<ref name="pmid12353193">{{cite journal| author=Gnann JW| title=Varicella-zoster virus: atypical presentations and unusual complications. | journal=J Infect Dis | year= 2002 | volume= 186 Suppl 1 | issue= | pages= S91-8 | pmid=12353193 | doi=10.1086/342963 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12353193 }} </ref>
*[[Fever]]
*[[Headache]]
*[[Ataxia|Loss of body control]]
*[[Aphasia|Inability to produce or comprehend language]]
*[[Seizure]]s
*[[Cough]]
*[[Dyspnea|Shortness of breath or labored breathing]]
*[[Hemoptysis|Coughing up blood]]
*[[Rash]]
*[[Lethargy]]

===Physical Examination===
Common physical examination findings of VZV encephalitis include:<ref name="pmid12353193">{{cite journal| author=Gnann JW| title=Varicella-zoster virus: atypical presentations and unusual complications. | journal=J Infect Dis | year= 2002 | volume= 186 Suppl 1 | issue= | pages= S91-8 | pmid=12353193 | doi=10.1086/342963 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12353193 }} </ref>
*[[Fever]]
*[[Aphasia]]
*[[Ataxia]]
*[[Nuchal rigidity]]
*[[Nystagmus]]
*[[Hypertonia]] or [[hypotonia]]
*[[Hyperreflexia]] or [[hyporeflexia]]
*Positive [[plantar reflex]]es
*[[Hemiparesis]]

If [[rash]] and [[ataxia]] are present simultaneously, the clinical presentation is sufficient to establish a diagnosis.

===Laboratory Findings===
Rapid diagnostic methods, which include [[polymerase chain reaction]] (PCR) and [[direct fluorescent antibody]] (DFA) assay, are the methods of choice. Polymerase chain reaction testing, the most sensitive test for VZV, can be used for detecting [[invasive]] disease, and detects varicella zoster virus in [[cytoplasm|vesicle fluid]], [[serum]], [[cerebrospinal fluid]], and other tissues. Direct fluorescent antibody assay is performed on scrapings taken from the base of a skin lesion, and is a rapid and reliable method for diagnosing VZV disease.<ref name="pmid20070670">{{cite journal| author=Pergam SA, Limaye AP, AST Infectious Diseases Community of Practice| title=Varicella zoster virus (VZV) in solid organ transplant recipients. | journal=Am J Transplant | year= 2009 | volume= 9 Suppl 4 | issue= | pages= S108-15 | pmid=20070670 | doi=10.1111/j.1600-6143.2009.02901.x | pmc=PMC2919834 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20070670 }} </ref> Cerebrospinal fluid analysis is essential (unless contraindicated) in all patients with encephalitis.<ref name=IDSAEnceph> The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America. http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Encephalitis.pdf Accessed on February 16, 2016.</ref> Therefore, [[lumbar puncture]] may be warranted. Laboratory findings consistent with the diagnosis of VZV encephalitis include [[leukocytosis]] and [[pleocytosis]].<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref>

===CT===
[[Computed tomography]] may be helpful in the diagnosis of VZV encephalitis. Findings on [[CT]] suggestive of VZV encephalitis include subtle low density within the [[anterior]] and [[medial]] [[temporal lobe]] and the [[insular cortex]].<ref name=RadioHSE> Herpes simplex encephalitis. Radiopaedia.org (2016). http://radiopaedia.org/articles/herpes-simplex-encephalitis Accessed on February 9, 2016. </ref> Subtleties become more apparent over time and may progress to [[hemorrhage]], and may eventually spread to the other [[temporal lobe]] after 7-10 days.<ref name="pmid11853816">{{cite journal |author=Whitley RJ, Gnann JW |title=Viral encephalitis: familiar infections and emerging pathogens |journal=Lancet |volume=359 |issue=9305 |pages=507–13 |year=2002 |pmid=11853816 |doi=}}</ref>

===MRI===
[[Magnetic resonance imaging]] is the imaging modality of choice for VZV encephalitis. Findings on [[MRI]] suggestive of VZV encephalitis include:<ref name=RadioHSE> Herpes simplex encephalitis. Radiopaedia.org (2016). http://radiopaedia.org/articles/herpes-simplex-encephalitis Accessed on February 9, 2016. </ref><ref name="pmid18319155">{{cite journal| author=Bulakbasi N, Kocaoglu M| title=Central nervous system infections of herpesvirus family. | journal=Neuroimaging Clin N Am | year= 2008 | volume= 18 | issue= 1 | pages= 53-84; viii | pmid=18319155 | doi=10.1016/j.nic.2007.12.001 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18319155 }} </ref>
*T1
**General [[edema]] in the affected region
**Hyperintense signal if complicated by subacute [[hemorrhage]]
*T1 C+ (Gd)
**Early, enhancement is generally absent
**Later, enhancement is variable and may appear as:
***Gyral enhancement
***[[Leptomeningeal]] enhancement
***Ring enhancement
***Diffuse enhancement
*T2
**Hyperintensity of affected [[white matter]] and [[cerebral cortex]]
*DWI/ADC
**More sensitive than T2 weighted images
**Restricted diffusion is common due to [[cytotoxic]] [[edema]]
*GE/SWI
**May demonstrate blooming if hemorrhagic

[[Image:VZV_Encephalitis_MRI_T2.jpeg|VZV Encephalitis MRI T2]]

===Lumbar Puncture===
Cerebrospinal fluid analysis is essential (unless contraindicated) in all patients with encephalitis.<ref name=IDSAEnceph> The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America. http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Encephalitis.pdf Accessed on February 16, 2016.</ref> Therefore, lumbar puncture may be helpful in the diagnosis of VZV encephalitis. Findings on lumbar puncture suggestive of VZV encephalitis include [[pleocytosis]].<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref>

==Treatment==
===Medical Therapy===
The mainstay of therapy for VZV encephalitis is [[antiviral]] therapy. [[Acyclovir]] is the drug of choice to treat VZV encephalitis. [[Ganciclovir]] and adjunctive [[corticosteroid]]s can be considered as alternatives.<ref name=IDSAEnceph> The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America. http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Encephalitis.pdf Accessed on February 16, 2016.</ref>

===Prevention===
[[Varicella vaccine]] or [[zostavax]] is recommended for the most individuals to prevent VZV encephalitis. Other primary prevention strategies include avoiding contact with affected individuals, [[disinfectant|disinfecting surfaces]], and [[hand washing]].

==References==
{{reflist|2}}

[[Category:Primary care]]
[[Category:Viral diseases]]
[[Category:Infectious disease]]
[[Category:Neurology]]

VZV encephalitis

2016-04-20T14:57:30Z

Sergekorjian: /* Differentiating VZV Encephalitis from Other Diseases */

__NOTOC__
{{CMG}} {{AE}} {{AG}}

{{SK}} Varicella zoster virus encephalitis; Herpes zoster encephalitis; Varicella zoster encephalitis; Varicella encephalitis;

==Overview==
VZV encephalitis is a viral infection of the [[central nervous system]]. Based on the duration of symptoms, VZV encephalitis may be classified into either acute or chronic. The exact pathogenesis of VZV encephalitis is not fully understood. The [[immune system]] eliminates the virus from most locations upon initial infection, but it remains [[viral latency|latent]] in the [[dorsal root ganglion]] and the [[trigeminal]] ganglion near the base of the [[skull]]. VZV encephalitis may be caused by either varicella ([[chickenpox]]) or herpes zoster ([[shingles]]). VZV encephalitis must be differentiated from other diseases that cause [[fever]], [[headache]], [[vomiting]], and [[altered mental status]]. The incidence of VZV encephalitis is approximately 10 per 100,000 individuals affected with [[varicella]], most often [[neonates]] and the [[elderly]].<ref name="pmid7658062">{{cite journal| author=Choo PW, Donahue JG, Manson JE, Platt R| title=The epidemiology of varicella and its complications. | journal=J Infect Dis | year= 1995 | volume= 172 | issue= 3 | pages= 706-12 | pmid=7658062 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7658062 }} </ref> If left untreated, [[immunocompromised]] patients with VZV encephalitis may progress to [[mortality]]. Common complications include [[shock]], [[hypoxemia]], and [[meningitis]]. Signs of VZV encephalitis include [[fever]], [[headache]], [[ataxia]], and [[aphasia]]. Laboratory findings consistent with the diagnosis of VZV encephalitis include [[leukocytosis]] and [[pleocytosis]].<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref> [[Magnetic resonance imaging]] is the imaging modality of choice for VZV encephalitis. [[Acyclovir]] is the drug of choice to treat VZV encephalitis.

==Classification==
Based on the duration of symptoms, VZV encephalitis may be classified into either acute or chronic.

==Pathophysiology==
The exact pathogenesis of VZV encephalitis is not fully understood. It is known that VZV encephalitis is the result of the [[varicella zoster virus]], a double-stranded [[DNA virus]] within the [[Herpesviridae]] family of viruses.<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref> The [[immune system]] eliminates the virus from most locations upon initial infection, but it remains [[viral latency|latent]] in the [[dorsal root ganglion]] and the [[trigeminal]] ganglion near the base of the [[skull]]. Initial infection by VZV presents as [[chickenpox]], often in children between the ages of 1-9. VZV reactivation, which presents as [[shingles]] in adults, is the result of a decline in the frequency of VZV-specific [[T cell]]s.<ref name="pmid9300702">{{cite journal| author=Sadzot-Delvaux C, Kinchington PR, Debrus S, Rentier B, Arvin AM| title=Recognition of the latency-associated immediate early protein IE63 of varicella-zoster virus by human memory T lymphocytes. | journal=J Immunol | year= 1997 | volume= 159 | issue= 6 | pages= 2802-6 | pmid=9300702 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9300702 }} </ref> The molecular basis of reactivation remains unknown.<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref> Some histopathologic studies suggest of a postinfectious [[demyelinating]] process, while other findings cite direct viral cytopathology.<ref name="pmid6326714">{{cite journal| author=Bauman ML, Bergman I| title=Postvaricella encephalitis. | journal=Arch Neurol | year= 1984 | volume= 41 | issue= 5 | pages= 556-8 | pmid=6326714 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6326714 }} </ref><ref name="pmid4311227">{{cite journal| author=McCormick WF, Rodnitzky RL, Schochet SS, McKee AP| title=Varicella-Zoster encephalomyelitis. A morphologic and virologic study. | journal=Arch Neurol | year= 1969 | volume= 21 | issue= 6 | pages= 559-70 | pmid=4311227 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4311227 }} </ref><ref name="pmid582251">{{cite journal| author=Takashima S, Becker LE| title=Neuropathology of fatal varicella. | journal=Arch Pathol Lab Med | year= 1979 | volume= 103 | issue= 5 | pages= 209-13 | pmid=582251 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=582251 }} </ref>

==Causes==
VZV encephalitis may be caused by either varicella ([[chickenpox]]) or herpes zoster ([[shingles]]).

==Differentiating VZV Encephalitis from Other Diseases==
VZV encephalitis must be differentiated from other diseases that cause [[fever]], [[headache]], [[vomiting]], and [[altered mental status]], such as:<ref name="pmid14978145">{{cite journal| author=Kennedy PG| title=Viral encephalitis: causes, differential diagnosis, and management. | journal=J Neurol Neurosurg Psychiatry | year= 2004 | volume= 75 Suppl 1 | issue= | pages= i10-5 | pmid=14978145 | doi= | pmc=PMC1765650 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14978145 }} </ref><ref name="pmid12353193">{{cite journal| author=Gnann JW| title=Varicella-zoster virus: atypical presentations and unusual complications. | journal=J Infect Dis | year= 2002 | volume= 186 Suppl 1 | issue= | pages= S91-8 | pmid=12353193 | doi=10.1086/342963 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12353193 }} </ref><ref name="pmid13065322">{{cite journal| author=APPELBAUM E, RACHELSON MH, DOLGOPOL VB| title=Varicella encephalitis. | journal=Am J Med | year= 1953 | volume= 15 | issue= 2 | pages= 223-30 | pmid=13065322 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13065322 }} </ref>

{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
|+
! style="background: #4479BA; width: 120px;" | {{fontcolor|#FFF|Disease}}
! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|Findings}}
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Herpes simplex encephalitis]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Viral encephalitis]] presents with acute [[inflammation]] of the [[brain]], caused by a [[viral infection]]; complications include severe [[brain]] damage as the inflamed [[brain]] pushes against the [[skull]], potentially leading to [[mortality]]. Other findings include [[fever]], [[confusion]], and [[aphasia]].
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Meningitis]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Meningitis]] presents with [[headache]], [[altered mental status]], and [[inflammation]] of the [[meninges]]. It may have an indolent evolution, resolving on its own, or may present as an rapidly evolving [[inflammation]], causing neurologic damage and possible [[mortality]]. {{see also|Bacterial meningitis|Viral meningitis|Fungal meningitis}}
|-
| style="padding: 5px 5px; background: #DCDCDC;" |'''[[Brain abscess]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Brain abscess]] presents with an [[abscess]] in the [[brain]] caused by the [[inflammation]] and accumulation of [[infected]] material from local or remote infectious areas of the body; the infectious agent may also be introduced as a result of head [[trauma]] or [[neurosurgery|neurological procedures]].
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Acute disseminated encephalomyelitis]] (ADEM)'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Acute disseminated encephalomyelitis]] presents with scattered foci of [[demyelination]] and perivenular [[inflammation]]; it can cause focal neurological signs and decreased ability to focus.
|-
|}

==Epidemiology and Demographics==
===Incidence===
The incidence of VZV encephalitis is approximately 10 per 100,000 individuals affected with [[varicella]].<ref name="pmid7658062">{{cite journal| author=Choo PW, Donahue JG, Manson JE, Platt R| title=The epidemiology of varicella and its complications. | journal=J Infect Dis | year= 1995 | volume= 172 | issue= 3 | pages= 706-12 | pmid=7658062 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7658062 }} </ref>

===Age===
VZV encephalitis most commonly affects infants or the [[elderly]].<ref name="pmid7658062">{{cite journal| author=Choo PW, Donahue JG, Manson JE, Platt R| title=The epidemiology of varicella and its complications. | journal=J Infect Dis | year= 1995 | volume= 172 | issue= 3 | pages= 706-12 | pmid=7658062 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7658062 }} </ref>

===Gender===
Men and women are affected equally by VZV encephalitis.

==Risk Factors==
Common risk factors in the development of VZV encephalitis include:<ref name="pmid12353193">{{cite journal| author=Gnann JW| title=Varicella-zoster virus: atypical presentations and unusual complications. | journal=J Infect Dis | year= 2002 | volume= 186 Suppl 1 | issue= | pages= S91-8 | pmid=12353193 | doi=10.1086/342963 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12353193 }} </ref><ref name="Mounsey">{{cite journal|title=Herpes zoster and postherpetic neuralgia: prevention and management|author=Mounsey AL, Matthew LG, & Slawson DC|date=2005|journal=American Family Physician|volume=72|issue=6|pages=1075-1080|pmid=16190505|url=http://www.aafp.org/afp/20050915/1075.html|accessdate=2007-06-15}}</ref><ref>{[cite journal|title=What does epidemiology tell us about risk factors for herpes zoster?|author=Thomas SL, Hall AJ|journal= Lancet Infect Dis.|date=2004|volume=4|issue=1|pages=26-33|pmid= 14720565}}</ref><ref name=IDSAEnceph> The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America. http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Encephalitis.pdf Accessed on February 16, 2016.</ref>
*[[Varicella zoster virus]] infection
*[[Immunosuppression]]
*[[HIV]] or [[AIDS]]
*[[Age]] extremes
*[[Stress]]
*Chronic [[corticosteroid]] usage
*[[Skin]] [[inflammation]]
*[[Pregnancy]]
*Living in tropical climate
*Working as a [[physician]] or other [[health care provider]]
*Absence of [[varicella vaccine]]

==Natural History, Complications, and Prognosis==
===Natural History===
Herpes zoster usually clears in 2 to 3 weeks and rarely recurs. However, if left untreated, [[immunocompromised]] patients with VZV encephalitis may progress to [[mortality]].

===Complications===
Common complications of VZV encephalitis include:<ref name="pmid14978145">{{cite journal| author=Kennedy PG| title=Viral encephalitis: causes, differential diagnosis, and management. | journal=J Neurol Neurosurg Psychiatry | year= 2004 | volume= 75 Suppl 1 | issue= | pages= i10-5 | pmid=14978145 | doi= | pmc=PMC1765650 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14978145 }} </ref>
*[[Shock]]
*[[Hypoxemia]]
*[[Hypotension]]
*[[Aphasia]]
*[[Seizures]]
*[[Meningitis]]
*Loss of [[motor skill]]s
*[[Coma]]
*[[Mortality]]

===Prognosis===
Prognosis for VZV encephalitis is generally good in most individuals. Prognosis for VZV encephalitis is poor in [[immunocompromised]] individuals.

==Diagnosis==
===History and Symptoms===
If possible, a detailed and thorough history from the patient is necessary. Symptoms of VZV encephalitis include:<ref name="pmid12353193">{{cite journal| author=Gnann JW| title=Varicella-zoster virus: atypical presentations and unusual complications. | journal=J Infect Dis | year= 2002 | volume= 186 Suppl 1 | issue= | pages= S91-8 | pmid=12353193 | doi=10.1086/342963 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12353193 }} </ref>
*[[Fever]]
*[[Headache]]
*[[Ataxia|Loss of body control]]
*[[Aphasia|Inability to produce or comprehend language]]
*[[Seizure]]s
*[[Cough]]
*[[Dyspnea|Shortness of breath or labored breathing]]
*[[Hemoptysis|Coughing up blood]]
*[[Rash]]
*[[Lethargy]]

===Physical Examination===
Common physical examination findings of VZV encephalitis include:<ref name="pmid12353193">{{cite journal| author=Gnann JW| title=Varicella-zoster virus: atypical presentations and unusual complications. | journal=J Infect Dis | year= 2002 | volume= 186 Suppl 1 | issue= | pages= S91-8 | pmid=12353193 | doi=10.1086/342963 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12353193 }} </ref>
*[[Fever]]
*[[Aphasia]]
*[[Ataxia]]
*[[Nuchal rigidity]]
*[[Nystagmus]]
*[[Hypertonia]] or [[hypotonia]]
*[[Hyperreflexia]] or [[hyporeflexia]]
*Positive [[plantar reflex]]es
*[[Hemiparesis]]

If [[rash]] and [[ataxia]] are present simultaneously, the clinical presentation is sufficient to establish a diagnosis.

===Laboratory Findings===
Rapid diagnostic methods, which include [[polymerase chain reaction]] (PCR) and [[direct fluorescent antibody]] (DFA) assay, are the methods of choice. Polymerase chain reaction testing, the most sensitive test for VZV, can be used for detecting [[invasive]] disease, and detects varicella zoster virus in [[cytoplasm|vesicle fluid]], [[serum]], [[cerebrospinal fluid]], and other tissues. Direct fluorescent antibody assay is performed on scrapings taken from the base of a skin lesion, and is a rapid and reliable method for diagnosing VZV disease.<ref name="pmid20070670">{{cite journal| author=Pergam SA, Limaye AP, AST Infectious Diseases Community of Practice| title=Varicella zoster virus (VZV) in solid organ transplant recipients. | journal=Am J Transplant | year= 2009 | volume= 9 Suppl 4 | issue= | pages= S108-15 | pmid=20070670 | doi=10.1111/j.1600-6143.2009.02901.x | pmc=PMC2919834 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20070670 }} </ref> Cerebrospinal fluid analysis is essential (unless contraindicated) in all patients with encephalitis.<ref name=IDSAEnceph> The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America. http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Encephalitis.pdf Accessed on February 16, 2016.</ref> Therefore, [[lumbar puncture]] may be warranted. Laboratory findings consistent with the diagnosis of VZV encephalitis include [[leukocytosis]] and [[pleocytosis]].<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref>

===CT===
[[Computed tomography]] may be helpful in the diagnosis of VZV encephalitis. Findings on [[CT]] suggestive of VZV encephalitis include subtle low density within the [[anterior]] and [[medial]] [[temporal lobe]] and the [[insular cortex]].<ref name=RadioHSE> Herpes simplex encephalitis. Radiopaedia.org (2016). http://radiopaedia.org/articles/herpes-simplex-encephalitis Accessed on February 9, 2016. </ref> Subtleties become more apparent over time and may progress to [[hemorrhage]], and may eventually spread to the other [[temporal lobe]] after 7-10 days.<ref name="pmid11853816">{{cite journal |author=Whitley RJ, Gnann JW |title=Viral encephalitis: familiar infections and emerging pathogens |journal=Lancet |volume=359 |issue=9305 |pages=507–13 |year=2002 |pmid=11853816 |doi=}}</ref>

===MRI===
[[Magnetic resonance imaging]] is the imaging modality of choice for VZV encephalitis. Findings on [[MRI]] suggestive of VZV encephalitis include:<ref name=RadioHSE> Herpes simplex encephalitis. Radiopaedia.org (2016). http://radiopaedia.org/articles/herpes-simplex-encephalitis Accessed on February 9, 2016. </ref><ref name="pmid18319155">{{cite journal| author=Bulakbasi N, Kocaoglu M| title=Central nervous system infections of herpesvirus family. | journal=Neuroimaging Clin N Am | year= 2008 | volume= 18 | issue= 1 | pages= 53-84; viii | pmid=18319155 | doi=10.1016/j.nic.2007.12.001 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18319155 }} </ref>
*T1
**General [[edema]] in the affected region
**Hyperintense signal if complicated by subacute [[hemorrhage]]
*T1 C+ (Gd)
**Early, enhancement is generally absent
**Later, enhancement is variable and may appear as:
***Gyral enhancement
***[[Leptomeningeal]] enhancement
***Ring enhancement
***Diffuse enhancement
*T2
**Hyperintensity of affected [[white matter]] and [[cerebral cortex]]
*DWI/ADC
**More sensitive than T2 weighted images
**Restricted diffusion is common due to [[cytotoxic]] [[edema]]
*GE/SWI
**May demonstrate blooming if hemorrhagic

[[Image:VZV_Encephalitis_MRI_T2.jpeg|VZV Encephalitis MRI T2]]

===Lumbar Puncture===
Cerebrospinal fluid analysis is essential (unless contraindicated) in all patients with encephalitis.<ref name=IDSAEnceph> The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America. http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Encephalitis.pdf Accessed on February 16, 2016.</ref> Therefore, lumbar puncture may be helpful in the diagnosis of VZV encephalitis. Findings on lumbar puncture suggestive of VZV encephalitis include [[pleocytosis]].<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref>

==Treatment==
===Medical Therapy===
The mainstay of therapy for VZV encephalitis is [[antiviral]] therapy. [[Acyclovir]] is the drug of choice to treat VZV encephalitis. [[Ganciclovir]] and adjunctive [[corticosteroid]]s can be considered as alternatives.<ref name=IDSAEnceph> The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America. http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Encephalitis.pdf Accessed on February 16, 2016.</ref>

===Prevention===
[[Varicella vaccine]] or [[zostavax]] is recommended for the most individuals to prevent VZV encephalitis. Other primary prevention strategies include avoiding contact with affected individuals, [[disinfectant|disinfecting surfaces]], and [[hand washing]].

==References==
{{reflist|2}}

[[Category:Primary care]]
[[Category:Viral diseases]]
[[Category:Infectious disease]]
[[Category:Neurology]]

Western equine encephalitis

2016-04-20T14:55:39Z

Sergekorjian: /* Differentiating Western equine encephalitis from Other Diseases */

__NOTOC__
{{SI}}
{{CMG}} {{AE}} {{AG}}

{{SK}} WEE; WEEV; West equine encephalitis;

==Overview==
Western equine encephalitis is a mild to moderate infection of the [[central nervous system]]. Western equine encephalitis belongs to the Group IV positive-sense ssRNA virus within the ''[[Togaviridae]]'' family of viruses, and the genus ''[[Alphavirus]]''. Western equine encephalitis is closely related to [[eastern equine encephalitis]] virus and [[Venezuelan equine encephalitis]] virus. Western equine encephalitis virus is usually transmitted via [[mosquito]]s to the human host, primarily ''Culiseta melanura'' and ''Culex tarsalis''. Western equine encephalitis virus must be differentiated from other diseases that cause [[fever]], [[headache]], [[seizures]], and [[altered mental status]]. Western equine encephalitis was last observed in humans in the United States in 1999. Prognosis for western equine encephalitis is generally good; western equine encephalitis is considered more mild than [[eastern equine encephalitis]]. [[invasive|Neuroinvasive]] vs non-neuroinvasive western equine encephalitis can be differentiated based on both clinical and laboratory findings. The diagnostic method of choice for western equine encephalitis is laboratory testing. The positive presence of [[IgM]] [[antibody|antibodies]] is diagnostic of western equine encephalitis. There is no treatment for western equine encephalitis; the mainstay of therapy is supportive care. There are currently no human vaccines available for western equine encephalitis.

==Historical Perspective==
Western equine encephalitis was first identified by Karl Friedrich Meyer, an American scientist of Swiss origin, in 1930 following an epizootic outbreak in horses in the San Joaquin Valley in California.<ref name="pmid17834966">{{cite journal| author=Meyer KF, Haring CM, Howitt B| title=THE ETIOLOGY OF EPIZOOTIC ENCEPHALOMYELITIS OF HORSES IN THE SAN JOAQUIN VALLEY, 1930. | journal=Science | year= 1931 | volume= 74 | issue= 1913 | pages= 227-8 | pmid=17834966 | doi=10.1126/science.74.1913.227 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17834966 }} </ref>

==Classification==
Western equine encephalitis may be classified according to location of the disease into 2 subtypes: systemic or encephalitic. Western equine encephalitis may also be classified according to [[invasive|neuroinvasiveness]] of the disease into 2 subtypes: neuroinvasive and non-neuroinvasive. Western equine encephalitis belongs to the Group IV positive-sense ssRNA virus within the ''[[Togaviridae]]'' family of viruses, and the genus ''[[Alphavirus]]''. Western equine encephalitis is closely related to [[eastern equine encephalitis]] virus and [[Venezuelan equine encephalitis]] virus. Western equine encephalitis is known as an [[arbovirus]], or an arthropod-borne virus.

==Pathophysiology==
Western equine encephalitis virus is usually transmitted via [[mosquito]]s to the human host. Western equine encephalitis virus contains [[positive-sense ssRNA virus|positive-sense]] viral [[RNA]]; this RNA has its genome directly utilized as if it were mRNA, producing a single protein which is modified by host and viral proteins to form the various proteins needed for [[replication]]. The following table is a summary of the western equine encephalitis virus:<ref name=ViralZoneAlpha> Alphavirus. SIB Swiss Institute of Bioinformatics. http://viralzone.expasy.org/viralzone/all_by_species/625.html Accessed on March 15, 2016 </ref>

{| class="wikitable"
! style="text-align: center; font-weight: bold;" | Characteristic
! style="text-align: center; font-weight: bold;" | Data
|-
| Nucleic acid
| [[RNA]]
|-
| Sense
| [[positive-sense ssRNA virus|ssRNA(+)]]
|-
| Virion
| [[enveloped virus|Enveloped]]
|-
| [[Capsid]]
| Spherical
|-
| Symmetry
| Yes; T=4 [[icosahedral]]
|-
| Capsid [[monomers]]
| 240
|-
| Monomer length (diameter)
| 65-70 nm
|-
| Additional envelope information
| 80 spikes; each spike is a [[trimer]] of E1/E2 proteins
|-
| Genome shape
| Linear
|-
| Genome length
| 11-12 kb
|-
| [[Nucleotide]] cap
| Yes
|-
| [[Polyadenylation|Polyadenylated]] tail
| Yes
|-
| [[Incubation period]]
| 5-10 days
|}

Western equine encephalitis is contracted by the [[bite]] of an infected [[mosquito]], primarily ''Culiseta melanura'' and ''Culex tarsalis''. The virus is maintained in a cycle between either of the mosquitos and avian hosts in [[freshwater]] hardwood swamps. Neither are an important vector of western equine virus to humans because both feed almost exclusively on birds. Transmission to humans requires mosquito species capable of creating a "bridge" between infected birds and uninfected mammals, such as some ''[[Aedes]]'', ''Coquillettidia'', and other ''Culex'' species. The [[incubation period]] is 5-10 days.<ref name=WEEOhioPH> WESTERN EQUINE ENCEPHALITIS VIRUS DISEASE. Ohio Department of Health. http://www.odh.ohio.gov/pdf/IDCM/wee.pdf Accessed on March 22, 2016.</ref> Humans and horses are dead-end hosts for the virus, meaning there is an insufficient amount of western equine encephalitis virus in the blood stream to infect a mosquito. Many cases in horses are fatal. There is no known transmission between horses and humans.<ref name=EEEVILPubHealth> Eastern Equine Encephalitis Virus (EEEV). Illinois Department of Public Health (2010) http://www.idph.state.il.us/public/hb/hb_eee.htm Accessed on March 15, 2016. </ref> Recent studies have demonstrated other equine, such as mules and donkeys, and other animals, such as pigs, reptiles, amphibians, and rodents, can be infected.

Western equine encephalitis virus is transmitted in the following pattern:<ref name=ViralZoneAlpha> Alphavirus. SIB Swiss Institute of Bioinformatics. http://viralzone.expasy.org/viralzone/all_by_species/625.html Accessed on March 15, 2016 </ref>

#Attachment of the viral E [[glycoprotein]] to host receptors mediates [[clathrin|clathrin-mediated]] [[endocytosis]] of virus into the host cell.
#Fusion of [[biological membrane|virus membrane]] with the host [[cell membrane]]. RNA genome is released into the [[cytoplasm]].
#The [[positive-sense ssRNA virus]] is [[translate]]d into a [[polyprotein]], which is cleaved into non-structural proteins necessary for RNA synthesis ([[replication]] and [[transcription]]).
#[[Replication]] takes place in [[cytoplasm]]ic viral factories at the surface of [[endosome]]s. A [[dsRNA]] [[genome]] is synthesized from the genomic ssRNA(+).
#The [[dsRNA]] [[genome]] is [[transcribed]] thereby providing viral [[mRNA]]s (new ssRNA(+) genomes).
#Expression of the subgenomic RNA (sgRNA) gives rise to the structural proteins.
#Virus assembly occurs at the [[endoplasmic reticulum]].
#[[Virion]]s bud at the [[endoplasmic reticulum]], are transported to the [[Golgi apparatus]], and then exit the cell via the [[secretory pathway]].

==Causes==
Western equine encephalitis may be caused by western equine encephalitis virus.

==Differentiating Western equine encephalitis from Other Diseases==
Western equine encephalitis virus must be differentiated from other diseases that cause [[fever]], [[headache]], [[seizures]], and [[altered mental status]], such as:<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref><ref name="pmid14978145">{{cite journal| author=Kennedy PG| title=Viral encephalitis: causes, differential diagnosis, and management. | journal=J Neurol Neurosurg Psychiatry | year= 2004 | volume= 75 Suppl 1 | issue= | pages= i10-5 | pmid=14978145 | doi= | pmc=PMC1765650 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14978145 }} </ref><ref name=NYDeptofHealth> Arboviral Infections (arthropod-borne encephalitis, eastern equine encephalitis, St. Louis encephalitis, California encephalitis, Powassan encephalitis, West Nile encephalitis). New York State Department of Health (2006). https://www.health.ny.gov/diseases/communicable/arboviral/fact_sheet.htm Accessed on February 23, 2016 </ref>

{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
|+
! style="background: #4479BA; width: 120px;" | {{fontcolor|#FFF|Disease}}
! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|Findings}}
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Meningitis]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Meningitis]] presents with [[headache]], [[altered mental status]], and [[inflammation]] of the [[meninges]], which may develop in the setting of an [[infection]], physical injury, [[cancer]], or certain drugs; it may have an indolent evolution, resolving on its own, or may present as an rapidly evolving [[inflammation]], causing neurologic damage and possible [[mortality]]. {{see also|Bacterial meningitis|Viral meningitis|Fungal meningitis}}
|-
| style="padding: 5px 5px; background: #DCDCDC;" |'''[[Brain abscess]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Brain abscess]] presents with an [[abscess]] in the [[brain]] caused by the [[inflammation]] and accumulation of [[infected]] material from local or remote infectious areas of the body; the infectious agent may also be introduced as a result of head [[trauma]] or [[neurosurgery|neurological procedures]].
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Acute disseminated encephalomyelitis]] (ADEM)'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Acute disseminated encephalomyelitis]] presents with scattered foci of [[demyelination]] and perivenular [[inflammation]]; it can cause focal neurological signs and decreased ability to focus.
|-
|}

==Epidemiology and Demographics==
Between 1964-2012, there were 640 confirmed human cases in the United States; the last one was observed in 1999.<ref name=WEEOhioPH> WESTERN EQUINE ENCEPHALITIS VIRUS DISEASE. Ohio Department of Health. http://www.odh.ohio.gov/pdf/IDCM/wee.pdf Accessed on March 22, 2016.</ref> In April 2009, the last known Western equine encephalitis fatality occurred in Uruguay.<ref name="pmid21529429">{{cite journal| author=Delfraro A, Burgueño A, Morel N, González G, García A, Morelli J et al.| title=Fatal human case of Western equine encephalitis, Uruguay. | journal=Emerg Infect Dis | year= 2011 | volume= 17 | issue= 5 | pages= 952-4 | pmid=21529429 | doi=10.3201/eid1705.101068 | pmc=PMC3321764 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21529429 }} </ref> The case-fatality rate of western equine encephalitis is < 5%.<ref name=IDSAEnceph> The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America. http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Encephalitis.pdf Accessed on February 16, 2016.</ref>

===Age===
Western equine encephalitis is most commonly observed among children under 4 years of age and adults over 50 years of age.<ref name=IDSAEnceph> The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America. http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Encephalitis.pdf Accessed on February 16, 2016.</ref>

===Race===
There is no racial predilection for western equine encephalitis.

===Seasonal===
Western equine encephalitis is most commonly observed in the summer months.

===Geographic Distribution===
Western equine encephalitis virus has been observed in North, Central, and South America; most cases have been reported from the Great Plains and Western regions of the United States.

==Risk Factors==
Common risk factors in the development of western equine encephalitis are:
*[[Age]]
*[[Immunosuppression]]
*Residing or visiting woodland areas
*[[Mosquito]] contact
*Bird contact
*Horse contact
*Summer season
*Outdoor recreational activities

==Natural History, Complications and Prognosis==
===Natural History===
If left untreated, approximately 10% patients with western equine encephalitis may progress to develop a [[febrile]] [[prodrome]] followed by [[meningismus]], [[weakness]], [[tremor]]s, and [[altered mental status]].

===Complications===
Complications of western equine encephalitis include:
*[[Seizure]]s
*Loss of basic [[motor skill]]s
*Loss of [[coordination]]
*[[Meningitis]]

===Prognosis===
Prognosis for western equine encephalitis is generally good; western equine encephalitis is considered more mild than [[eastern equine encephalitis]].

==Diagnosis==
===Diagnostic criteria===
Neuroinvasive vs non-neuroinvasive western equine encephalitis can be differentiated based on both clinical and laboratory findings. These include:<ref name=WVPubHealth> Arboviral Infection: Surveillance Protocol (2016) West Virginia Department of Health and Human Resources: Bureau of Public Health (2016). http://www.dhhr.wv.gov/oeps/disease/Zoonosis/Mosquito/Documents/arbovirus/arbovirus-protocol.pdf Accessed on March 3, 2016 </ref><ref name=CDCCritArboInvasive> Arboviral diseases, neuroinvasive and non-neuroinvasive 2015 Case Definition. National Notifiable Diseases Surveillance System (NNDSS). Centers for Disease Control (2015). https://wwwn.cdc.gov/nndss/conditions/arboviral-diseases-neuroinvasive-and-non-neuroinvasive/case-definition/2015/ Accessed on March 31, 2016. </ref>

{| class="wikitable"
! style="text-align: center; font-weight: bold;" | Western Equine Encephalitis Subtype
! style="text-align: center; font-weight: bold;" | Clinical Presentation
! style="text-align: center; font-weight: bold;" | Laboratory Findings
|-
| style="font-style: italic;" | Neuroinvasive
|
:{{unicode|☑}} [[Meningitis]], [[encephalitis]], acute flaccid [[paralysis]], or other acute signs of central or peripheral neurologic dysfunction, as documented by a [[physician]] '''AND'''
:{{unicode|☑}} Absence of a more likely clinical explanation
|
:{{unicode|☑}} Isolation of [[virus]] from, or demonstration of specific viral [[antigen]] or [[nucleic acid in]], [[tissue]], [[blood]], [[cerebrospinal fluid]] (CSF) '''OR'''
:{{unicode|☑}} Four-fold or greater change in virus-specific quantitative antibody [[titer]]s in paired sera '''OR'''
:{{unicode|☑}} Virus-specific [[IgM]] antibodies in [[serum]] with confirmatory virus-specific neutralizing antibodies in the same or a later specimen '''OR'''
:{{unicode|☑}} Virus-specific [[IgM]] antibodies in [[cerebrospinal fluid]], with or without a reported [[pleocytosis]], and a negative result for other IgM antibodies in cerebrospinal fluid for arboviruses endemic to the region where exposure occurred
|-
| style="font-style: italic;" | Non-neuroinvasive
|
:{{unicode|☑}} [[Fever]] and [[chills]] as reported by the [[patient]] or a [[health care provider]] '''AND'''
:{{unicode|☑}} Absence of [[invasive|neuroinvasive]] disease '''AND'''
:{{unicode|☑}} Absence of a more likely clinical explanation
|
:{{unicode|☑}} Isolation of [[virus]] from, or demonstration of specific viral [[antigen]] or [[nucleic acid]] in, [[tissue]], [[blood]], or other body fluid, excluding [[cerebrospinal fluid]] '''OR'''
:{{unicode|☑}} Four-fold or greater change in virus-specific quantitative antibody [[titer]]s in paired sera '''OR'''
:{{unicode|☑}} Virus-specific [[IgM]] antibodies in [[serum]] with confirmatory virus-specific neutralizing antibodies in the same or a later specimen
|}

===History and Symptoms===
If possible, a detailed and thorough history from the patient is necessary. Common symptoms of western equine encephalitis include:<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref><ref name= NINDS> Meningitis and Encephalitis Fact Sheet. National Institute of Neurological Disorders and Stroke. National Institutes of Health (2015). http://www.ninds.nih.gov/disorders/encephalitis_meningitis/detail_encephalitis_meningitis.htm Accessed on February 9, 2015 </ref>
*[[Fever]]
*[[Chills]]
*[[Headache]]
*[[Fatigue]]
*[[myalgia|Muscle pain]]
*[[Dizziness]]
*[[Altered mental status]]

===Physical Examination===
Common physical examination findings of western equine encephalitis include:<ref name="pmid20551475">{{cite journal| author=Steele KE, Twenhafel NA| title=REVIEW PAPER: pathology of animal models of alphavirus encephalitis. | journal=Vet Pathol | year= 2010 | volume= 47 | issue= 5 | pages= 790-805 | pmid=20551475 | doi=10.1177/0300985810372508 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20551475 }} </ref>
*[[Fever]]
*[[Ataxia]]
*[[Seizure]]s
*[[Obtundation]]
*[[Myalgia]]
*[[myelitis|Acute flaccid myelitis]]
*[[Lethargy]]
*[[Meningism]]
*[[Photophobia]]
*[[Somnolence]]
*[[Coma]]
*[[Motor neuron]] dysfunction

===Laboratory Findings===
The diagnostic method of choice for western equine encephalitis is laboratory testing. The positive presence of [[IgM]] [[antibody|antibodies]] is diagnostic of western equine encephalitis. Other laboratory findings consistent with the diagnosis of western equine encephalitis include:<ref name=IDSAEnceph> The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America. http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Encephalitis.pdf Accessed on February 16, 2016.</ref>
*[[Serologic]] [[cross-reactivity]]
*Persistence of [[IgG]] and neutralizing [[antibody|antibodies]]
*Confirmation of arboviral-specific neutralizing antibodies in [[enzyme linked immunosorbent assay (ELISA)]]
*In [[cerebrospinal fluid]]:
**[[Pleocytosis]]
**Increased protein levels
**Normal to slightly elevated [[glucose]] levels

===Imaging Findings===
There are no imaging findings specifically associated with western equine encephalitis. [[MRI]] is the modality of choice to evaluate all types of encephalitis. Although the pattern of involvement varies, in general, sites of involvement include:<ref name=EncephGeneralMRI> Flavivirus encephalitis. Radiopaedia.org (2016). http://radiopaedia.org/articles/flavivirus-encephalitis Accessed on March 29, 2016. </ref>
*T2 hyperintensity in the [[basal ganglia]] and [[thalamus]]
*Restricted diffusion in the [[basal ganglia]] and [[thalamus]]
*[[Hemorrhage]] less frequently

==Treatment==
===Medical Therapy===
There is no treatment for western equine encephalitis; the mainstay of therapy is supportive care. Because supportive care is the only treatment for western equine encephalitis, physicians often do not request the tests required to specifically identify the western equine encephalitis virus.

===Surgery===
Surgical intervention is not recommended for the management of western equine encephalitis.

===Prevention===
There is no human vaccine for western equine encephalitis. There is a western equine encephalitis vaccine available for horses. In consultation with a veterinarian, vaccinate your horse(s) against the virus. Primary prevention strategies for western equine encephalitis include:<ref name=EEENYPubHealth> Eastern Equine Encephalitis (EEE). New York State Department of Public Health (2012). https://www.health.ny.gov/diseases/communicable/eastern_equine_encephalitis/fact_sheet.htm Accessed on March 15, 2016.</ref>
*Removal of [[standing water]]
*Screens on doors and windows
*When outdoors, wearing:
**Insect repellent containing [[DEET]]
**Long sleeves, pants; tucking in pants into high socks

==References==
{{Reflist|2}}

[[Category:Viruses]]
[[Category:Neurology]]
[[Category:Infectious disease]]

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La Crosse encephalitis

2016-04-20T14:52:59Z

Sergekorjian: /* Differentiating La Crosse encephalitis from Other Disases */

__NOTOC__
{{SI}}
{{CMG}} {{AE}} {{AG}}

{{SK}} LACV; LaCrosse virus; LAC encephalitis; Lax encephalitis

==Overview==
La Crosse encephalitis is a mild infection of the [[central nervous system]]. La Crosse encephalitis virus belongs to the Group V [[negative-sense ssRNA virus|negative-sense ssRNA family of viruses]]. La Crosse encephalitis virus is also known as an [[arbovirus]]. La Crosse encephalitis virus is usually transmitted via [[mosquito]]s to the human host. The amplification pattern of La Crosse encephalitis virus has been extensively studied. La Crosse encephalitis virus is contracted by the [[bite]] of an infected [[mosquito]], primarily ''Aedes triseriatus''. La Crosse encephalitis virus must be differentiated from other diseases that cause [[fever]], [[headache]], [[seizures]], and [[altered mental status]]. There are approximately 70-115 cases of La Crosse encephalitis virus per year in the United States, most commonly affecting infants and children between the ages of 6 months and 15 years old. La Crosse encephalitis virus usually clears in 1 to 2 weeks and rarely recurs. Less than 1% of cases result in [[mortality]]. The diagnostic method of choice for La Crosse encephalitis virus is laboratory testing. There is no treatment for La Crosse encephalitis virus; the mainstay of therapy is supportive care.

==Historical Perspective==
In 1963, the cause of La Crosse encephalitis was discovered near La Crosse, Wisconsin by the Hooper Foundation.<ref name=Neurovirology> Tselis AC, Booss J. Neurovirology, Handbook of Clinical Neurology Series (Series Editors: Aminoff, Boller, Swaab). Newnes; 2014.</ref> La Crosse encephalitis was first discovered within the brain during the [[autopsy]] of a 4 year old boy who died from encephalitis. Upon further microscopic histopathological analysis by Whitman and Shope, it was confirmed that the La Crosse encephalitis virus was genetically related to the [[California encephalitis virus]].<ref name="pmid14000396">{{cite journal| author=WHITMAN L, SHOPE RE| title=The California complex of arthropod-borne viruses and its relationship to the Bunyamwera group through Guaroa virus. | journal=Am J Trop Med Hyg | year= 1962 | volume= 11 | issue= | pages= 691-6 | pmid=14000396 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14000396 }} </ref><ref name="pmid14261030">{{cite journal| author=THOMPSON WH, KALFAYAN B, ANSLOW RO| title=ISOLATION OF CALIFORNIA ENCEPHALITIS GROUP VIRUS FROM A FATAL HUMAN ILLNESS. | journal=Am J Epidemiol | year= 1965 | volume= 81 | issue= | pages= 245-53 | pmid=14261030 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14261030 }} </ref>

==Classification==
La Crosse encephalitis may be classified according to [[invasive|neuroinvasiveness]] into 2 groups: neuroinvasive and non-neuroinvasive.<ref name=WVPubHealth> Arboviral Infection: Surveillance Protocol (2016) West Virginia Department of Health and Human Resources: Bureau of Public Health (2016). http://www.dhhr.wv.gov/oeps/disease/Zoonosis/Mosquito/Documents/arbovirus/arbovirus-protocol.pdf Accessed on March 3, 2016 </ref> La Crosse encephalitis virus belongs to the Group V [[negative-sense ssRNA virus]] within the [[Bunyaviridae]] family of viruses, and the genus [[Orthobunyavirus]]. La Crosse encephalitis virus is also known as an [[arbovirus]], or an arthropod-borne virus. The La Crosse virus is the principal member of the [[California encephalitis serogroup]], which contains genetically similar viruses such as [[California encephalitis virus]].<ref name=OHIOPubHealth> La Crosse Encephalitis. Ohio Department of Health. http://www.odh.ohio.gov/pdf/idcm/lac.pdf Accessed on March 1, 2016.</ref>

==Pathophysiology==
La Crosse encephalitis virus is usually transmitted via [[mosquito]]s to the human host. La Crosse encephalitis virus contains [[negative-sense ssRNA virus|negative-sense]] viral [[RNA]]; this RNA is [[complementary]] to [[mRNA]] and thus must be converted to [[positive-sense RNA]] by an [[RNA polymerase]] before [[translation]]. La Crosse encephalitis virus is made up of an [[enveloped virus|enveloped virion]] with a spherical [[capsid]]. The envelope contains G1 [[glycoprotein]]s. Neutralizing [[antibodies]] against these proteins block fusion of the virus with host cells and inhibit [[hemagglutination]]. The virus genome is over 12,000 [[nucleotide]]s in length, approximately 90-100 nm in diameter, and consists of three segments of various sized single-stranded [[RNA]] (negative sense and ambi-sense).<ref name=CDCLACV> La Crosse Encephalitis. Centers for Disease Control and Prevention (2009). http://www.cdc.gov/lac/ Accessed on March 1, 2016. </ref>

La Crosse encephalitis virus is contracted by the [[bite]] of an infected [[mosquito]], primarily ''Aedes triseriatus''. The virus is maintained and amplified in ''Aedes triseriatus'' populations through [[transovarial transmission|transovarial]] and [[venereal|venereal transmission]]. The virus overwinters in the mosquito egg. [[Amplification]] also occurs in chipmunks and squirrels, upon which mosquitos feed. Humans are dead-end hosts for the virus, meaning there is an insufficient amount of La Crosse encephalitis virus in the blood stream to infect a mosquito. Subsequently, the disease cannot be spread to other humans. The [[incubation period]] is 5-15 days.<ref name=OHIOPubHealth> La Crosse Encephalitis. Ohio Department of Health. http://www.odh.ohio.gov/pdf/idcm/lac.pdf Accessed on February 25, 2016.</ref>

La Crosse encephalitis virus is transmitted in the following pattern:<ref name=SIBSwiss> Bunyaviridae. SIB Swiss Institute of Bioinformatics http://viralzone.expasy.org/viralzone/all_by_species/82.html Accessed on March 1, 2016 </ref>
#Virus attaches to host receptors though Gn-Gc [[glycoprotein]] [[dimer]], and is [[endocytosis|endocytosed]] into [[Vesicle (biology)|vesicles]] in the [[Host (biology)|host cell]].
#Fusion of [[biological membrane|virus membrane]] with the [[cell membrane|vesicle membrane]]; ribonucleocapsid segments are released in the [[cytoplasm]].
#[[Transcription]] occurs; viral mRNAs are capped in the cytoplasm.
#[[Replication]] presumably begins when sufficient [[nucleoprotein]] is present to encapsidate neo-synthetized antigenomes and [[genome]]s.
#The ribonucleocapsids buds at [[Golgi apparatus]], releasing the virion by [[exocytosis]].

==Causes==
La Crosse encephalitis virus causes La Crosse encephalitis.

==Differentiating La Crosse encephalitis from Other Disases==
La Crosse encephalitis virus must be differentiated from other diseases that cause [[fever]], [[headache]], [[seizures]], and [[altered mental status]], such as:<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref><ref name="pmid14978145">{{cite journal| author=Kennedy PG| title=Viral encephalitis: causes, differential diagnosis, and management. | journal=J Neurol Neurosurg Psychiatry | year= 2004 | volume= 75 Suppl 1 | issue= | pages= i10-5 | pmid=14978145 | doi= | pmc=PMC1765650 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14978145 }} </ref><ref name=NYDeptofHealth> Arboviral Infections (arthropod-borne encephalitis, eastern equine encephalitis, St. Louis encephalitis, California encephalitis, Powassan encephalitis, West Nile encephalitis). New York State Department of Health (2006). https://www.health.ny.gov/diseases/communicable/arboviral/fact_sheet.htm Accessed on February 23, 2016 </ref><ref name=LACVMinnPH> La Crosse encephalitis fact sheet (2013). http://www.health.state.mn.us/divs/idepc/diseases/lacencephalitis/lc.html Accessed on March 1, 2016. </ref>

{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
|+
! style="background: #4479BA; width: 120px;" | {{fontcolor|#FFF|Disease}}
! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|Findings}}
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Meningitis]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Meningitis]] presents with [[headache]], [[altered mental status]], and [[inflammation]] of the [[meninges]], which may develop in the setting of an [[infection]], physical injury, [[cancer]], or certain drugs; it may have an indolent evolution, resolving on its own, or may present as an rapidly evolving [[inflammation]], causing neurologic damage and possible [[mortality]]. {{see also|Bacterial meningitis|Viral meningitis|Fungal meningitis}}
|-
| style="padding: 5px 5px; background: #DCDCDC;" |'''[[Brain abscess]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Brain abscess]] presents with an [[abscess]] in the [[brain]] caused by the [[inflammation]] and accumulation of [[infected]] material from local or remote infectious areas of the body; the infectious agent may also be introduced as a result of head [[trauma]] or [[neurosurgery|neurological procedures]].
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Acute disseminated encephalomyelitis]] (ADEM)'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Acute disseminated encephalomyelitis]] presents with scattered foci of [[demyelination]] and perivenular [[inflammation]]; it can cause focal neurological signs and decreased ability to focus.
|-
|}

==Epidemiology and Demographics==
===Incidence===
There are approximately 80-100 cases of La Crosse encephalitis per year in the United States. There is significant under-diagnosis and under-reporting of less severe cases of La Crosse encephalitis.<ref name=CDCLACV> La Crosse Encephalitis. Centers for Disease Control and Prevention (2009). http://www.cdc.gov/lac/ Accessed on March 1, 2016. </ref>

===Age===
La Crosse encephalitis commonly affects individuals between 6 months old and 15 years of age. Adults comprise the most under-diagnosed group.

===Seasonal===
The majority of La Crosse encephalitis cases are reported in the summer months between July and September, and peaks in August.

===Geographic Location===
The majority of La Crosse encephalitis cases are reported in the Midwestern United States, especially those living in rural and suburban settings surrounded by deciduous forests. Historically, most cases of La Crosse encephalitis occur in the Midwest states (Minnesota, Wisconsin, Iowa, Illinois, Indiana, and Ohio). Recently, more cases are being reported from states in the Southeast United States (Virginia, Virginia, North Carolina, Alabama and Mississippi).

Maps regarding geographic distribution of La Crosse encephalitis cases can be found [http://www.cdc.gov/lac/tech/epi.html here].

==Risk Factors==
Common risk factors in the development of La Crosse encephalitis virus include:
*Young [[age]]
*[[Immunosuppression]]
*Residing or working in rural and suburban settings
*[[Mosquito]] contact
*Summer season
*Outdoor activities such as camping or hunting

==Natural History, Complications, and Prognosis==
===Natural History===
La Crosse encephalitis virus usually clears in 1 to 2 weeks and rarely recurs. Less than 1% of cases result in [[mortality]].<ref name=OHIOPubHealth> La Crosse Encephalitis. Ohio Department of Health. http://www.odh.ohio.gov/pdf/idcm/lac.pdf Accessed on February 25, 2016.</ref>

===Complications===
Common complications of La Crosse encephalitis virus include:
*Recurring [[seizure]]s
*[[Coma]]
*Loss of basic [[motor skill]]s
*Loss of [[coordination]]

===Prognosis===
Prognosis for La Crosse encephalitis virus is generally good, with most individuals returning to full health in 2-3 weeks. However, approximately 20% of patients have [[residual]] [[seizure]]s.

==Diagnosis==
===Diagnostic Criteria===
Neuroinvasive vs non-neuroinvasive La Crosse encephalitis can be differentiated based on both clinical and laboratory findings. These include:<ref name=WVPubHealth> Arboviral Infection: Surveillance Protocol (2016) West Virginia Department of Health and Human Resources: Bureau of Public Health (2016). http://www.dhhr.wv.gov/oeps/disease/Zoonosis/Mosquito/Documents/arbovirus/arbovirus-protocol.pdf Accessed on March 3, 2016 </ref>

{| class="wikitable"
! style="text-align: center; font-weight: bold;" | La Crosse Encephalitis Subtype
! style="text-align: center; font-weight: bold;" | Clinical Presentation
! style="text-align: center; font-weight: bold;" | Laboratory Findings
|-
| style="font-style: italic;" | Neuroinvasive
|
:{{unicode|☑}} [[Meningitis]], [[encephalitis]], acute flaccid [[paralysis]], or other acute signs of central or peripheral neurologic dysfunction, as documented by a [[physician]] '''AND'''
:{{unicode|☑}} Absence of a more likely clinical explanation
|
:{{unicode|☑}} Isolation of [[virus]] from, or demonstration of specific viral [[antigen]] or [[nucleic acid in]], [[tissue]], [[blood]], [[cerebrospinal fluid]] (CSF) '''OR'''
:{{unicode|☑}} Four-fold or greater change in virus-specific quantitative antibody [[titer]]s in paired sera '''OR'''
:{{unicode|☑}} Virus-specific [[IgM]] antibodies in [[serum]] with confirmatory virus-specific neutralizing antibodies in the same or a later specimen '''OR'''
:{{unicode|☑}} Virus-specific [[IgM]] antibodies in [[cerebrospinal fluid]], with or without a reported [[pleocytosis]], and a negative result for other IgM antibodies in cerebrospinal fluid for arboviruses endemic to the region where exposure occurred
|-
| style="font-style: italic;" | Non-neuroinvasive
|
:{{unicode|☑}} [[Fever]] and [[chills]] as reported by the [[patient]] or a [[health care provider]] '''AND'''
:{{unicode|☑}} Absence of [[invasive|neuroinvasive]] disease '''AND'''
:{{unicode|☑}} Absence of a more likely clinical explanation
|
:{{unicode|☑}} Isolation of [[virus]] from, or demonstration of specific viral [[antigen]] or [[nucleic acid]] in, [[tissue]], [[blood]], or other body fluid, excluding [[cerebrospinal fluid]] '''OR'''
:{{unicode|☑}} Four-fold or greater change in virus-specific quantitative antibody [[titer]]s in paired sera '''OR'''
:{{unicode|☑}} Virus-specific [[IgM]] antibodies in [[serum]] with confirmatory virus-specific neutralizing antibodies in the same or a later specimen
|}

===History and Symptoms===
If possible, a detailed and thorough history from the patient is necessary. Common symptoms of La Crosse encephalitis include:<ref name=CDCLACV> La Crosse Encephalitis. Centers for Disease Control and Prevention (2009). http://www.cdc.gov/lac/ Accessed on March 1, 2016. </ref><ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref><ref name="pmid26595861">{{cite journal| author=Richie MB, Josephson SA| title=A Practical Approach to Meningitis and Encephalitis. | journal=Semin Neurol | year= 2015 | volume= 35 | issue= 6 | pages= 611-20 | pmid=26595861 | doi=10.1055/s-0035-1564686 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26595861 }} </ref>
*[[Fever]]
*[[Headache]]
*[[Nausea]]
*[[Vomiting]]
*[[Seizure]]s
*[[Altered mental status]]
*[[Fatigue]]
*[[Lethargy|Reduced alertness]]

===Physical Examination===
Common physical examination findings of La Crosse encephalitis include:<ref name=OHIOPubHealth> La Crosse Encephalitis. Ohio Department of Health. http://www.odh.ohio.gov/pdf/idcm/lac.pdf Accessed on February 25, 2016.</ref>
*[[Fever]]
*[[Ataxia]]
*[[Seizure]]s
*[[Somnolence]]
*[[Obtundation]]
*[[Myalgia]]
*[[myelitis|Acute flaccid myelitis]]
*[[Hemiparesis]]

===Laboratory Findings===
The diagnostic method of choice for La Crosse encephalitis is laboratory testing. Laboratory findings consistent with the diagnosis of La Crosse encephalitis include:<ref name=OHIOPubHealth> La Crosse Encephalitis. Ohio Department of Health. http://www.odh.ohio.gov/pdf/idcm/lac.pdf Accessed on February 25, 2016.</ref>
*[[Serologic]] [[cross-reactivity]]
*Presence of [[IgM]] [[antibody|antibodies]]
*Persistence of [[IgG]] and neutralizing [[antibody|antibodies]]
*Confirmation of arboviral-specific neutralizing antibodies in [[enzyme linked immunosorbent assay (ELISA)]]
*Mildly elevated [[white blood cell]] count
*Normal [[glucose]] levels

===CT===
There are no CT findings associated with La Crosse encephalitis.

===EEG===
On [[EEG]], La Crosse encephalitis virus is characterized by periodic lateralizing epilepitoform discharges.<ref name="pmid18160548">{{cite journal| author=de los Reyes EC, McJunkin JE, Glauser TA, Tomsho M, O'Neal J| title=Periodic lateralized epileptiform discharges in La Crosse encephalitis, a worrisome subgroup: clinical presentation, electroencephalogram (EEG) patterns, and long-term neurologic outcome. | journal=J Child Neurol | year= 2008 | volume= 23 | issue= 2 | pages= 167-72 | pmid=18160548 | doi=10.1177/0883073807307984 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18160548 }} </ref> However, results on imaging are not sufficient evidence to warrant La Crosse encephalitis virus diagnosis. In rare cases, EEG findings may resemble [[herpes simplex encephalitis]].

==Treatment==
===Medical Therapy===
There is no treatment for La Crosse encephalitis; the mainstay of therapy is supportive care. Because supportive care is the only treatment for La Crosse encephalitis, physicians often do not request the tests required to specifically identify the La Crosse encephalitis virus. These cases may be reported as aseptic meningitis or viral encephalitis of unknown etiology.<ref name=IDSAEnceph> The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America. http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Encephalitis.pdf Accessed on February 16, 2016.</ref>

===Surgery===
Surgical intervention is not recommended for the management of La Crosse encephalitis.

===Prevention===
There are no available vaccines against La Crosse encephalitis virus. Primary prevention strategies include:<ref name=OHIOPubHealth> La Crosse Encephalitis. Ohio Department of Health. http://www.odh.ohio.gov/pdf/idcm/lac.pdf Accessed on February 25, 2016.</ref>
*Removal of [[standing water]]
*Screens on doors and windows
*When outdoors, wearing:
**Insect repellent containing [[DEET]]
**Long sleeves, pants; tucking in pants into high socks

==Gallery==
<gallery>

Image: Bunyaviridae08.jpeg| This electron micrograph reveals the morphologic traits of the La Crosse encephalitis virus, a Bunyaviridae virus family member. ''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref>

Image: Bunyaviridae07.jpeg| This negatively-stained transmission electron micrograph (TEM) revealed the presence of La Crosse encephalitis virus ribonucleoprotein particles (RNP). ''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref>

Image: Bunyaviridae05.jpeg| This negatively-stained transmission electron micrograph (TEM) revealed the presence of La Crosse encephalitis virus ribonucleoprotein particles (RNP). ''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref>

</gallery>

==References==
{{reflist|2}}

[[Category:Viruses]]
[[Category:Neurology]]
[[Category:Infectious disease]]

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

Appendicitis surgery

2016-04-20T13:18:20Z

Sergekorjian: /* Surgical Procedure */

__NOTOC__
{{Appendicitis}}
{{CMG}}; {{AE}} {{FH}}
==Overview==
Surgery is the mainstay of therapy for appendicitis. Either a [[laparoscopic]] approach or an open [[appendectomy]] is recommended.

==Surgery==
===Surgical Procedure===
*Both the [[laparoscopic]] approach or open [[appendectomy]] is associated with low morbidity and mortality.<ref name="pmid23294512">{{cite journal| author=Sartelli M, Viale P, Catena F, Ansaloni L, Moore E, Malangoni M et al.| title=2013 WSES guidelines for management of intra-abdominal infections. | journal=World J Emerg Surg | year= 2013 | volume= 8 | issue= 1 | pages= 3 | pmid=23294512 | doi=10.1186/1749-7922-8-3 | pmc=PMC3545734 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23294512 }} </ref>
*If the stomach is empty (no food in the past six hours) general anesthesia is usually used. Otherwise, spinal anesthesia can also be used.
*There are two types of surgeries used to treat appendicitis: open and laparoscopic appendectomies.
*In 1983, when the first described minimally invasive laparoscopic appendectomy was completed, surgical procedures began to shift away from the open appendectomy towards laparoscopic procedures.<ref name="pmid10">{{cite journal |vauthors=Switzer, Noah J., Gill, Richdeep S., Karmali, Shahzeer|title=The Evolution of the Appendectomy: From Open to Laparoscopic to Single Incision|journal=Scientifica. |volume=2012|pages=1-5 |year=2012 |pmid=10 |doi=10.6064/2012/895469 |url=http://www.hindawi.com/journals/scientifica/2012/895469/}}</ref>
====Open Appendectomy====
*The open appendectomy is the conventional approach for removing the appendix during surgery, though more recently, surgeons and patients both prefer the laparoscopic approach.<ref name="pmid10">{{cite journal |vauthors=Switzer, Noah J., Gill, Richdeep S., Karmali, Shahzeer|title=The Evolution of the Appendectomy: From Open to Laparoscopic to Single Incision|journal=Scientifica. |volume=2012|pages=1-5 |year=2012 |pmid=10 |doi=10.6064/2012/895469 |url=http://www.hindawi.com/journals/scientifica/2012/895469/}}</ref>
*In the open procedures, a 5 cm incision is made in the at the lateral border of the right rectus muscle in the [[abdomen]], and the [[appendix]] is surgically removed.<ref name="pmid10">{{cite journal |vauthors=Switzer, Noah J., Gill, Richdeep S., Karmali, Shahzeer|title=The Evolution of the Appendectomy: From Open to Laparoscopic to Single Incision|journal=Scientifica. |volume=2012|pages=1-5 |year=2012 |pmid=10 |doi=10.6064/2012/895469 |url=http://www.hindawi.com/journals/scientifica/2012/895469/}}</ref>
====Laparoscopic Surgery====
*In the [[laparoscopic surgery]], three small incisions are made in the abdomen with a small camera inserted to visualize the area of interest in the abdomen.
*Surgical tools are fed through [[trocar]]s to minimize unnecessary surgical incisions in the patient. The appendix is surgically removed and taken out of the body through one of the small incisions.
**If the findings reveal [[suppuration|suppurative]] appendicitis with complications such as rupture, abscess, adhesions, etc., conversion to an open [[laparotomy]] may be necessary.
**Open laparotomy incisions most often center on the area of maximum tenderness, [[McBurney's point]], in the right lower quadrant of the abdomen.<ref name="urlAppendicitis">{{cite web |url=http://www.cs.mcgill.ca/~rwest/link-suggestion/wpcd_2008-09_augmented/wp/a/Appendicitis.htm |title=Appendicitis |format= |work= |accessdate=November 30, 2015}}</ref>

===Comparison of Surgical Treatments===
*The open appendectomy is still considered the gold standard in complicated appendicitis because of increased intra-abdominal infectious complications during the post-operative period.
*The open appendectomy is a intraoperative backup plan for the laparoscopy approach when there is severe appendiceal inflammation or any other forms of adhesions from previous surgeries.
*The preference from a laparoscopic to an open appendectomy is 8.6%, yet this number is decreasing as surgeons become attuned to the laparoscopic approach.
*In patients under the age of 5 or those who are pregnant, [[laparotomy]] is preferred because the abdomen is too small for the requirements of a laparoscopy or the risk to the fetus is too high.<ref name="pmid10">{{cite journal |vauthors=Switzer, Noah J., Gill, Richdeep S., Karmali, Shahzeer|title=The Evolution of the Appendectomy: From Open to Laparoscopic to Single Incision|journal=Scientifica. |volume=2012|pages=1-5 |year=2012 |pmid=10 |doi=10.6064/2012/895469 |url=http://www.hindawi.com/journals/scientifica/2012/895469/}}</ref>
*Young female, obese, and employed patients seem to benefit from the laparoscopic procedure more than other groups.<ref name="pmid15495014">{{cite journal |author=Sauerland S, Lefering R, Neugebauer EA |title=Laparoscopic versus open surgery for suspected appendicitis |journal=Cochrane Database Syst Rev |volume= |issue=4 |pages=CD001546 |year=2004 |pmid=15495014 |doi=10.1002/14651858.CD001546.pub2}}</ref>
*[[Laparoscopic surgery]] has resulted in decreased hospital stay, reduced risk of wound infection, reduced post-operative pain, and a faster return to daily activities for the patient.<ref name="urlAppendicitis">{{cite web |url=http://www.cs.mcgill.ca/~rwest/link-suggestion/wpcd_2008-09_augmented/wp/a/Appendicitis.htm |title=Appendicitis |format= |work= |accessdate=November 30, 2015}}</ref>

==References==
{{reflist|2}}
[[Category:Primary care]]
[[Category:emergency medicine]]
[[Category:Inflammations]]
[[Category:Medical emergencies]]
[[Category:General surgery]]
[[Category:Gastroenterology]]
[[Category:Disease]]
{{WH}}
{{WS}}

Appendicitis surgery

2016-04-20T13:18:01Z

Sergekorjian:

__NOTOC__
{{Appendicitis}}
{{CMG}}; {{AE}} {{FH}}
==Overview==
Surgery is the mainstay of therapy for appendicitis. Either a [[laparoscopic]] approach or an open [[appendectomy]] is recommended.

==Surgery==
===Surgical Procedure===
*Both the [[laparoscopic]] approach or open [[appendicectomy]] is associated with low morbidity and mortality.<ref name="pmid23294512">{{cite journal| author=Sartelli M, Viale P, Catena F, Ansaloni L, Moore E, Malangoni M et al.| title=2013 WSES guidelines for management of intra-abdominal infections. | journal=World J Emerg Surg | year= 2013 | volume= 8 | issue= 1 | pages= 3 | pmid=23294512 | doi=10.1186/1749-7922-8-3 | pmc=PMC3545734 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23294512 }} </ref>
*If the stomach is empty (no food in the past six hours) general anesthesia is usually used. Otherwise, spinal anesthesia can also be used.
*There are two types of surgeries used to treat appendicitis: open and laparoscopic appendectomies.
*In 1983, when the first described minimally invasive laparoscopic appendectomy was completed, surgical procedures began to shift away from the open appendectomy towards laparoscopic procedures.<ref name="pmid10">{{cite journal |vauthors=Switzer, Noah J., Gill, Richdeep S., Karmali, Shahzeer|title=The Evolution of the Appendectomy: From Open to Laparoscopic to Single Incision|journal=Scientifica. |volume=2012|pages=1-5 |year=2012 |pmid=10 |doi=10.6064/2012/895469 |url=http://www.hindawi.com/journals/scientifica/2012/895469/}}</ref>
====Open Appendectomy====
*The open appendectomy is the conventional approach for removing the appendix during surgery, though more recently, surgeons and patients both prefer the laparoscopic approach.<ref name="pmid10">{{cite journal |vauthors=Switzer, Noah J., Gill, Richdeep S., Karmali, Shahzeer|title=The Evolution of the Appendectomy: From Open to Laparoscopic to Single Incision|journal=Scientifica. |volume=2012|pages=1-5 |year=2012 |pmid=10 |doi=10.6064/2012/895469 |url=http://www.hindawi.com/journals/scientifica/2012/895469/}}</ref>
*In the open procedures, a 5 cm incision is made in the at the lateral border of the right rectus muscle in the [[abdomen]], and the [[appendix]] is surgically removed.<ref name="pmid10">{{cite journal |vauthors=Switzer, Noah J., Gill, Richdeep S., Karmali, Shahzeer|title=The Evolution of the Appendectomy: From Open to Laparoscopic to Single Incision|journal=Scientifica. |volume=2012|pages=1-5 |year=2012 |pmid=10 |doi=10.6064/2012/895469 |url=http://www.hindawi.com/journals/scientifica/2012/895469/}}</ref>
====Laparoscopic Surgery====
*In the [[laparoscopic surgery]], three small incisions are made in the abdomen with a small camera inserted to visualize the area of interest in the abdomen.
*Surgical tools are fed through [[trocar]]s to minimize unnecessary surgical incisions in the patient. The appendix is surgically removed and taken out of the body through one of the small incisions.
**If the findings reveal [[suppuration|suppurative]] appendicitis with complications such as rupture, abscess, adhesions, etc., conversion to an open [[laparotomy]] may be necessary.
**Open laparotomy incisions most often center on the area of maximum tenderness, [[McBurney's point]], in the right lower quadrant of the abdomen.<ref name="urlAppendicitis">{{cite web |url=http://www.cs.mcgill.ca/~rwest/link-suggestion/wpcd_2008-09_augmented/wp/a/Appendicitis.htm |title=Appendicitis |format= |work= |accessdate=November 30, 2015}}</ref>

===Comparison of Surgical Treatments===
*The open appendectomy is still considered the gold standard in complicated appendicitis because of increased intra-abdominal infectious complications during the post-operative period.
*The open appendectomy is a intraoperative backup plan for the laparoscopy approach when there is severe appendiceal inflammation or any other forms of adhesions from previous surgeries.
*The preference from a laparoscopic to an open appendectomy is 8.6%, yet this number is decreasing as surgeons become attuned to the laparoscopic approach.
*In patients under the age of 5 or those who are pregnant, [[laparotomy]] is preferred because the abdomen is too small for the requirements of a laparoscopy or the risk to the fetus is too high.<ref name="pmid10">{{cite journal |vauthors=Switzer, Noah J., Gill, Richdeep S., Karmali, Shahzeer|title=The Evolution of the Appendectomy: From Open to Laparoscopic to Single Incision|journal=Scientifica. |volume=2012|pages=1-5 |year=2012 |pmid=10 |doi=10.6064/2012/895469 |url=http://www.hindawi.com/journals/scientifica/2012/895469/}}</ref>
*Young female, obese, and employed patients seem to benefit from the laparoscopic procedure more than other groups.<ref name="pmid15495014">{{cite journal |author=Sauerland S, Lefering R, Neugebauer EA |title=Laparoscopic versus open surgery for suspected appendicitis |journal=Cochrane Database Syst Rev |volume= |issue=4 |pages=CD001546 |year=2004 |pmid=15495014 |doi=10.1002/14651858.CD001546.pub2}}</ref>
*[[Laparoscopic surgery]] has resulted in decreased hospital stay, reduced risk of wound infection, reduced post-operative pain, and a faster return to daily activities for the patient.<ref name="urlAppendicitis">{{cite web |url=http://www.cs.mcgill.ca/~rwest/link-suggestion/wpcd_2008-09_augmented/wp/a/Appendicitis.htm |title=Appendicitis |format= |work= |accessdate=November 30, 2015}}</ref>

==References==
{{reflist|2}}
[[Category:Primary care]]
[[Category:emergency medicine]]
[[Category:Inflammations]]
[[Category:Medical emergencies]]
[[Category:General surgery]]
[[Category:Gastroenterology]]
[[Category:Disease]]
{{WH}}
{{WS}}

Appendicitis risk factors

2016-04-20T13:14:20Z

Sergekorjian: /* In Children */

__NOTOC__
{{Appendicitis}}
{{CMG}}; {{AE}} {{FH}}

==Overview==
Identifying risk factors that predict the likelihood of complications is a crucial step in managing appendicitis. Appendicitis is most common among people in the age group of 10 to 30 years old. Appendicitis leads to more emergency abdominal surgeries than any other cause.

==Risk Factors==
*The most common cases of appendicitis occur between the ages of 10 and 30 years, and it is the most likely cause of acute abdomen pain in the United States, with a 5-20% chance of lifetime risk.<ref name="urlAppendicitis - The University of Chicago Medicine">{{cite web |url=http://www.uchospitals.edu/online-library/content=P00815 |title=Appendicitis - The University of Chicago Medicine |format= |work= |accessdate=November 30, 2015}}</ref><ref name="pmid12832966">{{cite journal |vauthors=Margenthaler JA, Longo WE, Virgo KS, Johnson FE, Oprian CA, Henderson WG, Daley J, Khuri SF |title=Risk factors for adverse outcomes after the surgical treatment of appendicitis in adults |journal=Ann. Surg. |volume=238 |issue=1 |pages=59–66 |year=2003 |pmid=12832966 |pmc=1422654 |doi=10.1097/01.SLA.0000074961.50020.f8 |url=}}</ref>

===In Adults===
Common risk factors for adults include:<ref name="pmid12832966">{{cite journal |vauthors=Margenthaler JA, Longo WE, Virgo KS, Johnson FE, Oprian CA, Henderson WG, Daley J, Khuri SF |title=Risk factors for adverse outcomes after the surgical treatment of appendicitis in adults |journal=Ann. Surg. |volume=238 |issue=1 |pages=59–66 |year=2003 |pmid=12832966 |pmc=1422654 |doi=10.1097/01.SLA.0000074961.50020.f8 |url=}}</ref>
*[[Steroid]] use
*[[Diabetes]]
*Chronic obstructive [[pulmonary disease]]

===In Children===
Common risk factors in children include:<ref name="urlAppendicitis - The University of Chicago Medicine">{{cite web |url=http://www.uchospitals.edu/online-library/content=P00815 |title=Appendicitis - The University of Chicago Medicine |format= |work= |accessdate=November 30, 2015}}</ref>
*Appendicitis results in the most common need for emergency abdominal surgery.
*A family history of appendicitis increases the child's risk, especially in males.
**Male children with [[cystic fibrosis]] are at an even higher risk.

==References==
{{reflist|2}}
{{WH}}
{{WS}}
[[Category:Primary care]]
[[Category:emergency medicine]]
[[Category:Inflammations]]
[[Category:Medical emergencies]]
[[Category:General surgery]]
[[Category:Gastroenterology]]
[[Category:Disease]]
[[Category:Needs content]]

Appendicitis pathophysiology

2016-04-20T13:12:15Z

Sergekorjian:

__NOTOC__
{{Appendicitis}}
{{CMG}}; {{AE}} {{FH}}

==Overview==
Appendicitis is caused by the obstruction of the [[Lumen (anatomy)|tubular space]] inside the [[appendix]]. This initial problem is compounded into a cascade of events that lead to the [[inflammation]] of the [[appendix]], the [[obstruction]] of the blood vessels supplying it, and [[infection]]. Once these blood vessels are obstructed, appendiceal tissue starts to die and leak out its cellular components.
==Pathophysiology==
===Pathogenesis===
*On the basis of experimental evidence, acute appendicitis is the end result of a primary obstruction of the appendiceal [[lumen]].<ref> Wangensteen OH, Bowers WF. Significance of the obstructive factor in the genesis of acute appendicitis. Arch Surg 1937;34:496-526 </ref>
*Appendiceal luminar obstructions are a common inciting event leading to inflammation.<ref name="book1">{{Citation
| last1 = Yelon
| first1 = Jay A.
| last2 = Luchette
| first2 = Fred A.
| lastauthoramp = yes
| title = Geriatric Trauma and Critical Care
| publisher = Springer
| place = New York, New York
| edition = 1st
| year = 2014
}}</ref>
**Appendiceal obstructions can be caused by:<ref name="book1">{{Citation
| last1 = Yelon
| first1 = Jay A.
| last2 = Luchette
| first2 = Fred A.
| lastauthoramp = yes
| title = Geriatric Trauma and Critical Care
| publisher = Springer
| place = New York, New York
| edition = 1st
| year = 2014
}}</ref>
*** [[Fecaliths]]
*** [[Lymphoid Hyperplasia]]
*** Benign or malignant [[tumors]]
*** Infectious processes
** Obstructions can lead to an increase in [[endoluminar]] and [[intramural]] pressure, which can result in an occlusion of the [[venules]] in the appendiceal wall.
*** The [[appendix]] can fill with [[mucus]] and distends.
***The increase in pressure leads to [[thrombosis]] and [[occlusion]] of the small vessels, and stasis of lymphatic flow.

===Associated Conditions===
Associated conditions of appendicitis include:<ref name="book1">{{Citation
| last1 = Yelon
| first1 = Jay A.
| last2 = Luchette
| first2 = Fred A.
| lastauthoramp = yes
| title = Geriatric Trauma and Critical Care
| publisher = Springer
| place = New York, New York
| edition = 1st
| year = 2014
}}</ref>
* [[Intestinal obstruction]]
* [[Inflammatory bowel disease]]
* [[Pelvic inflammatory disease]] and other gynecological disorders
* Intestinal [[adhesions]]
* [[Constipation]]

===Gross Pathology===
* Inflammation of the appendiceal wall can result in [[perforation]] and development of a contained [[abscess]] or generalized [[peritonitis]].
*The wall of the [[appendix]] can become ischemic as vascular and lymphatic [[occlusion]] progress.<ref name="book1">{{Citation
| last1 = Yelon
| first1 = Jay A.
| last2 = Luchette
| first2 = Fred A.
| lastauthoramp = yes
| title = Geriatric Trauma and Critical Care
| publisher = Springer
| place = New York, New York
| edition = 1st
| year = 2014
}}</ref>

==References==
{{reflist|2}}
[[Category:Primary care]]
[[Category:emergency medicine]]
[[Category:Inflammations]]
[[Category:Medical emergencies]]
[[Category:General surgery]]
[[Category:Gastroenterology]]
[[Category:Disease]]
{{WH}}
{{WS}}

Surface epithelial-stromal tumor

2016-04-20T13:07:22Z

Sergekorjian:

__NOTOC__
{{SI}}
{{CMG}} {{AE}} {{MV}}

{{SK}} Borderline ovarian tumors; Ovarian epithelial neoplasms

==Overview==
'''Surface epithelial-stromal tumors''' are a class of [[Ovarian cancer|ovarian neoplasm]]s that may be [[benign]] or [[malignant]]. [[Neoplasm]]s in this group are thought to be derived from the [[ovarian surface epithelium]] (modified [[peritoneum]]) or from [[:wikt:ectopic|ectopic]] [[endometrial]] or [[Fallopian tube]] (tubal) tissue. This group of tumors accounts for 90% to 95% of all cases of [[ovarian cancer]].<ref>{{cite book |author=Bradshaw, Karen D.; Schorge, John O.; Schaffer, Joseph; Lisa M. Halvorson; Hoffman, Barbara G. |title=Williams' Gynecology |publisher=McGraw-Hill Professional |location= |year=2008 |pages= |isbn=0-07-147257-6 |oclc= |doi= |accessdate=}}</ref><ref name="SEER6215ch16">{{Cite book|contribution=Chapter 16: Cancers of the Ovary|first=Carol L.|last=Kosary|pages=133–144|publisher=National Cancer Institute|title=SEER Survival Monograph: Cancer Survival Among Adults: US SEER Program, 1988-2001, Patient and Tumor Characteristics|editor1-last=Baguio|editor1-first=RNL|editor2-last=Young|editor2-first=JL|editor3-last=Keel|editor3-first=GE|editor4-last=Eisner|editor4-first=MP|editor5-last=Lin|editor5-first=YD|editor6-last=Horner|editor6-first=M-J|series=SEER Program|volume=NIH Pub. No. 07-6215|place=Bethesda, MD|year=2007|chapterurl=http://seer.cancer.gov/publications/survival/surv_ovary.pdf|url=http://seer.cancer.gov/publications/survival/}}</ref> The pathogenesis of surface epithelial-stromal tumor is characterized by the overgrowth of the ovarian surface epithelium. Common risk factors in the development of surface epithelial-stromal tumor, include: nulliparity, [[Menopause|early menopause]], [[Gonadal dysgenesis, XY female type|gonadal dysgenesis]], family history (e.g. [[BRCA1|BRCA1/BRCA2]] mutations), smoking, previous history of breast, and endometrial or colon cancer ([[Hereditary nonpolyposis colorectal cancer|Lynch]] II). The prevalence of surface epithelial-stromal tumor is approximately 3 per 100,000 individuals worldwide. Surface epithelial-stromal tumor is more commonly observed among postmenopausal women. Early clinical features of surface epithelial-stromal tumor include pelvic fullness, abdominal distension, and abdominal pain. The mainstay of therapy for surface epithelial-stromal tumor is [[Chemotherapy|platinum-based chemotherapy]]. According to the American College of Radiology, secondary prevention of surface epithelial-stromal tumor may include periodical pelvis or transvaginal ultrasound with or without Doppler.<ref name="wiki">Surface epithelial-stromal tumor. Wikipedia. https://en.wikipedia.org/wiki/Surface_epithelial-stromal_tumor Accessed on April 18, 2016 </ref>

==Historical Perspective==
*Surface epithelial-stromal tumor was first discovered by Taylor in 1929.

==Classification==
*Surface epithelial-stromal tumor may be classified according to the World Health Organization (WHO) into 5 subtypes:<ref name="wiki">Surface epithelial-stromal tumor. Wikipedia. https://en.wikipedia.org/wiki/Surface_epithelial-stromal_tumor Accessed on April 18, 2016 </ref>
:*[[Mucinous tumor|Mucinous tumors]]
:*Endometroid tumors
:*[[Clear cell tumor|Clear cell tumors]]
:*[[Brenner tumor|Brenner tumors]]
:*Small cell tumors

==Pathophysiology==
*The pathogenesis of surface epithelial-stromal tumor is characterized by the overgrowth of the ovarian surface epithelium.
*The HYAL1-3 mutation has been associated with the development of surface epithelial-stromal tumor.
*On gross pathology, characteristic findings of surface epithelial-stromal tumor, include:<ref name="wiki">Surface epithelial-stromal tumor. Wikipedia. https://en.wikipedia.org/wiki/Surface_epithelial-stromal_tumor Accessed on April 18, 2016 </ref>
:*Complex multiloculated mass with mucin.
:*Often large - may > 30 cm.
*On microscopic histopathological analysis, characteristic findings of surface epithelial-stromal tumor, include:<ref name="wiki">Surface epithelial-stromal tumor. Wikipedia. https://en.wikipedia.org/wiki/Surface_epithelial-stromal_tumor Accessed on April 18, 2016 </ref><ref name="pmid1869263">{{cite journal |vauthors=Bell DA |title=Ovarian surface epithelial-stromal tumors |journal=Hum. Pathol. |volume=22 |issue=8 |pages=750–62 |year=1991 |pmid=1869263 |doi= |url=}}</ref>
:*Lined by tall, columnar, ciliated epithelial cells
:*Filled with clear serous fluid
:*The presence of '''[[Psammoma body|psammoma bodies]]'''
:*May involve the surface of the ovary
:*The division between benign, borderline, and malignant is ascertained by assessing:
:*[[Atypia|Cellular atypia]] (whether or not individual cells look abnormal)
:*Invasion of surrounding ovarian stroma (whether or not cells are infiltrating surrounding tissue)
:*Borderline tumors may have cellular atypia but do '''not''' have evidence of invasion

==Causes==
*Causes of surface epithelial-stromal tumor, include:<ref name="wiki">Surface epithelial-stromal tumor. Wikipedia. https://en.wikipedia.org/wiki/Surface_epithelial-stromal_tumor Accessed on April 18, 2016 </ref>
:*Mucinous tumors
:*Endometroid tumors
:*Clear cell tumors
:*Brenner tumors
:*Small cell tumors

==Differentiating Surface Epithelial-Stromal Tumor from Other Diseases==
*Surface epithelial-stromal tumor must be differentiated from other diseases that cause abdominal distension, pelvic or abdominal pain, and nausea, such as:<ref name="wiki">Surface epithelial-stromal tumor. Wikipedia. https://en.wikipedia.org/wiki/Surface_epithelial-stromal_tumor Accessed on April 18, 2016 </ref><ref name="pmid1869263">{{cite journal |vauthors=Bell DA |title=Ovarian surface epithelial-stromal tumors |journal=Hum. Pathol. |volume=22 |issue=8 |pages=750–62 |year=1991 |pmid=1869263 |doi= |url=}}</ref>
:*[[Dysgerminoma|Ovarian dysgerminoma]]
:*[[Yolk sac tumor|Ovarian yolk sac tumor]]
:*Ovarian embryonal carcinoma

==Epidemiology and Demographics==

*The prevalence of surface epithelial-stromal tumor is approximately 3 per 100,000 individuals worldwide.
*In 2011, the delay-adjusted [[incidence]] of surface epithelial-stromal tumor was estimated to be 12.46 per 100,000 persons in the United States.<ref name="SEER">Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.</ref>
*In the United States, the age-adjusted [[prevalence]] of surface epithelial-stromal tumor is 71.3 per 100,000 in 2011.<ref name="SEER">Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.</ref>

===Age===
*Patients of all age groups may develop surface epithelial-stromal tumor.
*Surface epithelial-stromal tumor is more commonly observed among patients aged 55 to 75 years old.
*Surface epithelial-stromal tumor is more commonly observed among postmenopausal women.

===Gender===
*Surface epithelial-stromal tumor only affects women.

===Race===
*There is no racial predilection for surface epithelial-stromal tumor.

==Risk Factors==
*Common risk factors in the development of surface epithelial-stromal tumor, include:<ref name="wiki">Surface epithelial-stromal tumor. Wikipedia. https://en.wikipedia.org/wiki/Surface_epithelial-stromal_tumor Accessed on April 18, 2016 </ref>
:*Nulliparity
:*Early menopause
:*Gonadal dysgenesis
:*Family history (e.g. BRCA1/BRCA2 mutations)
:*Smoking
:*Previous history of breast, endometrial or colon cancer (Lynch II)

*Common protective factors in the development of surface epithelial-stromal tumor, include:<ref name="wiki">Surface epithelial-stromal tumor. Wikipedia. https://en.wikipedia.org/wiki/Surface_epithelial-stromal_tumor Accessed on April 18, 2016 </ref>
:*Oral contraceptives

== Natural History, Complications and Prognosis==
*The majority of patients with surface epithelial-stromal tumor remain asymptomatic for years.<ref name="pmid1869263">{{cite journal |vauthors=Bell DA |title=Ovarian surface epithelial-stromal tumors |journal=Hum. Pathol. |volume=22 |issue=8 |pages=750–62 |year=1991 |pmid=1869263 |doi= |url=}}</ref>
*Early clinical features of surface epithelial-stromal tumor include pelvic fullness, abdominal distension, and abdominal pain.
*If left untreated, the minority of patients with surface epithelial-stromal tumor may progress to develop local invasion, lymphadenopathy, ascites, or metastases.
*Common complications of surface epithelial-stromal tumor include peritoneal metastases, or ovarian torsion.<ref name="wiki">Surface epithelial-stromal tumor. Wikipedia. https://en.wikipedia.org/wiki/Surface_epithelial-stromal_tumor Accessed on April 18, 2016 </ref>
*Prognosis will depend on tumor histology. In general, the 10-year survival rate of patients with surface epithelial-stromal tumor is approximately 66% - 90%

== Diagnosis ==
===Diagnostic Criteria===
*The diagnosis of surface epithelial-stromal tumor when the following diagnostic criteria are met:<ref name="pmid1869263">{{cite journal |vauthors=Bell DA |title=Ovarian surface epithelial-stromal tumors |journal=Hum. Pathol. |volume=22 |issue=8 |pages=750–62 |year=1991 |pmid=1869263 |doi= |url=}}</ref>
:*Imaging findings compatible with ovarian mass.
:*Elevated levels of [[CA-125]]
:*Present clinical criteria
::*Increased abdominal distension

=== Symptoms ===
*Surface epithelial-stromal tumor is usually asymptomatic.
*Symptoms of surface epithelial-stromal tumor may include the following:<ref name="wiki">Surface epithelial-stromal tumor. Wikipedia. https://en.wikipedia.org/wiki/Surface_epithelial-stromal_tumor Accessed on April 18, 2016 </ref><ref name="pmid1869263">{{cite journal |vauthors=Bell DA |title=Ovarian surface epithelial-stromal tumors |journal=Hum. Pathol. |volume=22 |issue=8 |pages=750–62 |year=1991 |pmid=1869263 |doi= |url=}}</ref>
:*[[Abdominal pain]]
:*[[Dyspareunia]]
:*[[Nausea]]
:*[[Vomiting]]

=== Physical Examination ===
*Patients with surface epithelial-stromal tumor usually are well-appearing.
*Pelvic and abdominal examination may be remarkable for:<ref name="wiki">Surface epithelial-stromal tumor. Wikipedia. https://en.wikipedia.org/wiki/Surface_epithelial-stromal_tumor Accessed on April 18, 2016 </ref>
:*Increased [[abdominal distension]]
:*"Wave sign" ascities
:*Decreased breath sounds

=== Laboratory Findings ===
*Laboratory findings consistent with the diagnosis of surface epithelial-stromal tumor, include:<ref name="wiki">Surface epithelial-stromal tumor. Wikipedia. https://en.wikipedia.org/wiki/Surface_epithelial-stromal_tumor Accessed on April 18, 2016 </ref><ref name="pmid1869263">{{cite journal |vauthors=Bell DA |title=Ovarian surface epithelial-stromal tumors |journal=Hum. Pathol. |volume=22 |issue=8 |pages=750–62 |year=1991 |pmid=1869263 |doi= |url=}}</ref>
:*Elevated CA-125 level
::*Often unspecific
::*Useful for treatment response

===Imaging Findings===
*Pelvic transabdominal/transvaginal ultrasound with or without Doppler is the initial imaging method of choice for surface epithelial-stromal tumor.
*Enhanced CT is the imaging modality of choice for surface epithelial-stromal tumor.
*On ultrasound, findings of surface epithelial-stromal tumor, include:<ref name="pmid1869263">{{cite journal |vauthors=Bell DA |title=Ovarian surface epithelial-stromal tumors |journal=Hum. Pathol. |volume=22 |issue=8 |pages=750–62 |year=1991 |pmid=1869263 |doi= |url=}}</ref>
:*Hypoechoic/hyperechoic solid mass
:*Calcification
*On CT, findings of surface epithelial-stromal tumor, include:
:*Calcifications
:*Solid component may show mild to moderate enhancement post contrast.
:*Large mass
*On MRI, findings of surface epithelial-stromal tumor, include
:*Hypointense on T2 weighted sequences

== Treatment ==
=== Medical Therapy ===
*The mainstay of therapy for surface epithelial-stromal tumor is platinum-based chemotherapy.<ref name="pmid1869263">{{cite journal |vauthors=Bell DA |title=Ovarian surface epithelial-stromal tumors |journal=Hum. Pathol. |volume=22 |issue=8 |pages=750–62 |year=1991 |pmid=1869263 |doi= |url=}}</ref>

=== Surgery ===
*Surgery is the mainstay of therapy for surface epithelial-stromal tumor.

=== Prevention ===
*There are no primary preventive measures available for surface epithelial-stromal tumor.
*A controversial measure for the primary prevention of surface epithelial-stromal tumor may include oral contraceptives.
*According to the American College of Radiology, secondary prevention of surface epithelial-stromal tumor may include periodical pelvis or transvaginal ultrasound with or without Doppler.

==Gallery==
[[Image:lmp_dry.jpg|thumb|left|Ovarian surface papillary serous tumor of low malignant potential.Courtesy of Ed Uthman, MD]]
[[Image:ovary_serous_ca.jpg|thumb|center|Serous cystadenocarcinoma of the ovary. Courtesy of Ed Uthman, MD]]

==References==
{{Reflist|2}}

[[Category: Oncology]]

Saphenous vein graft failure as a Surrogate Endpoint in Clinical Trials

2016-04-20T12:25:33Z

Sergekorjian:

{{SI}}
{{CMG}}

==Overview==
One issue that arises is the suitability of SVG patency, and SVG narrowing as a [[surrogate endpoint]] for clinical events. A '''surrogate marker''' (or '''surrogate end point''') is term used in medical research for a change to the [[human body]] that is believe to be necessary to an eventual outcome or '''end point'''.<ref>{{cite journal
| author = Cohn JN
| title = Introduction to Surrogate Markers
| journal = Circulation
| volume = 109
| pages = IV20–1
| publisher = American Heart Association
| date = 2004
| url = http://circ.ahajournals.org/cgi/content/full/109/25_suppl_1/IV-20
| accessdate = 2007-01-10
| pmid=15226247
}}</ref>
In [[clinical trial]]s, a '''surrogate endpoint''' is a measure of the effect (often what is known as a biomarker like cholesterol) of a certain treatment that is substituted in the evaluation of a new drug or device in place of a "hard endpoint" like death or heart attack. The [[National Institutes of Health]] (USA) defines surrogate endpoints as: "A biomarker intended to substitute for a clinical endpoint".<ref>Controlled Clinical Trials 22:485–502 (2001))</ref> The use of a surrogate endpoint can lead to more rapid and efficient completion of clinical trials, but the use of a surrogate endpoint has been criticized as reductions of a substitute maker are not always predictive of improvements in clinical outcomes. The classic example of a failed surrogate marker is the use of PVC suppression as a substitute marker of anti-arrhythmia effectiveness. Class III anti-arrhythmias reduced [[PVC]]s or extra heart beats, but were associated with a higher risk of death in the Cardiac Arrhythmia Suppression Trial (CAST)<ref name="pmid10147539">{{cite journal | author = Naccarelli GV, Dougherty AH, Wolbrette D, Wiggins S | title = A critical appraisal of the cardiac arrhythmia suppression trial (CAST) | journal = [[Applied Cardiopulmonary Pathophysiology : ACP]] | volume = 4 | issue = 1 | pages = 9–16 | year = 1991 | pmid = 10147539 | doi = | url = | issn = | accessdate = 2010-10-31}}</ref>. Surrogate markers may be used when it is unethical to look for the end point (e.g., death) in the experiment, or when the number of end point events is very small, thus making it impractical to conduct an experiment to look for the end point. The measurement of surrogate markers provides a way to test the effectiveness of a treatment for a fatal disease without having to wait for a [[statistical significance|statistically significant]] number of deaths to occur. The [[Food and Drug Administration|FDA]] will often accept evidence from [[clinical trial]]s that show a benefit with respect to surrogate markers instead of hard clinical end points.

==The Advantages of a Surrogate Endpoint==
The assessment of "hard" primary clinical endpoints (such as death and heart attack) often requires large long-term clinical trials which can be quite expensive. The use of surrogate endpoints can allow trials to evaluate the efficacy of a new drug or device more rapidly, more efficiently and more inexpensively.

==The Disadvantages of Surrogate Endpoints==
There are several potential disadvantages of a surrogate endpoint.

1. The surrogate endpoint may intuitively be hypothesized to be related to a "hard endpoint" such as death or [[heart attack]], but may not be.

2. While a surrogate endpoint may be related to a "hard endpoint" such as death or [[heart attack]], it is not clear that a '''''reduction''''' in the surrogate endpoint will lead to an improvement in the "hard endpoint" in death or [[heart attack]]. Anti-diabetic agents have been shown to reduce long term glucose (Hemoglobin A1c or HbA1C). It was hypothesized that more intense glucose control (a reduction in HbA1C) would be associated with a lower rate of death and heart attack. However, despite lowering of HbA1C, [[rosiglitazone]] or [[Avandia]] was not associated with a reduction in death and MI, but with an increase in the RECORD trial <ref name="pmid19501900">{{cite journal | author = Home PD, Pocock SJ, Beck-Nielsen H, Curtis PS, Gomis R, Hanefeld M, Jones NP, Komajda M, McMurray JJ | title = Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial | journal = [[Lancet]] | volume = 373 | issue = 9681 | pages = 2125–35 | year = 2009 | month = June | pmid = 19501900 | doi = 10.1016/S0140-6736(09)60953-3 | url = http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(09)60953-3 | issn = | accessdate = 2010-10-31}}</ref> <ref name="pmid20332408">{{cite journal | author = Nissen SE | title = Setting the RECORD Straight | journal = [[JAMA : the Journal of the American Medical Association]] | volume = 303 | issue = 12 | pages = 1194–5 | year = 2010 | month = March | pmid = 20332408 | doi = 10.1001/jama.2010.333 | url = http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=20332408 | issn = | accessdate = 2010-10-31}}</ref>.

In another example, class III antiarrhythmic agents were associated with suppression of [[premature ventricular contractions]] or [[PVC]]s, but were associated with a higher rate of death.

3. While a surrogate endpoint may be related to a "hard endpoint, it may be an acausal association (the surrogate may not lie in the causal pathway to the "hard endpoint" and changing the surrogate endpoint may not change the "hard endpoint".)

4. The agent may reduce the surrogate endpoint, but due to off target toxicity, may increase the risk of "hard endpoints" such as death or [[MI]]. Lower [[HDL]] is associated with a higher risk of adverse cardiac outcomes, [[Torcetrapib]] raises [[HDL]] and should therefore improve clinical outcomes, however, [[Torcetrapib]] administration was found to be associated with a higher rate of adverse clinical outcomes. It was felt that the potential benefit of [[Torcetrapib]] was reversed due to off target toxicity of a slight increase in [[blood pressure]] associated with [[Torcetrapib]] administration.

5. The relationship between the surrogate endpoint and the "hard endpoint" may be non-linear or may be a threshold effect. For example, in antiplatelet agent studies, it is unclear if ever greater levels of inhibition of platelet aggregation are associated with ever greater reductions in adverse outcomes, or if one must achieve just a certain "threshold" level of inhibition to improve outcomes.

There have been a number of instances when studies using surrogate markers have been used to show benefit from a particular treatment, but later, a repeat study looking at endpoints has not shown a benefit, or even a harm.<ref>{{cite journal|author=Psaty BM, Weiss NS, Furberg CD, ''et al.''|title=Surrogate end points, health outcomes, and the drug approval process for the treatment of risk factors for cardiovascular disease|journal=JAMA|year=1999|volume=282|pages=786–790}}</ref>

==Examples of Surrogate Endpoints==
Examples of surrogate markers include:
*Total [[cholesterol]]
*High density lipoprotein ([[HDL]])
*Low density lipoprotein ([[LDL]])
*[[c reactive protein]] ([[cRP]])
*Platelet inhibition by [[light transmittance aggregometry]]
*Coronary blood flow
*Minimum diameter or an artery and restenosis
* Fragmented blood cells are a surrogate marker for organ failure or stroke in [[thrombotic thrombocytopenic purpura|TTP]]
* The [[S phase|S-phase]] duration, may be used as a surrogate marker for breast cancer occurrence
* [[CD4]] count is a surrogate marker for death from HIV infection

==Evaluation of a Surrogate Endpoint==
A surrogate may be suitable as a surrogate endpoint if the following three criteria are satisfied:

#The drug or device improves the surrogate
#Improvement in the surrogate is related to an improvement in a hard clinical endpoint
#The same drug or device improves the hard clinical endpoint

In order for a surrogate to be validated, there must be at least one large clinical trial that satisfies these criteria. After this, other studies could rely upon the surrogate if it has been validated in a large study.

==Caveats in the use of SVG Failure as a Surrogate Endpoint==
There are multiple studies demonstrating that SVG closure or failure is associated with clinical events. The association of SVG failure or narrowing with clinical events is complex and should be interpreted in light of the following nuances:

#'''Often a composite endpoint of death, MI and revascularization is reported.''' One must be careful to deconstruct this composite endpoint to look at the association between SVG failure and each of these endpoints separately.
#It can be useful to distinguish between an MI that precedes and MI that follows revascularization to treat SVG failure. Understanding the timing of the myonecrosis allows one to undersantd the mechanism that caused the MI. An MI that precedes revascularization may be temporally attributable to the SVG failure itself, rather than the revascularization procedure to treat the SVG failure. A limitation to this assertion is that the release of markers of myonecrosis may be delayed, and a late rise in a cardiac biomarker may not be solely due to the revascularization, but it may also be related to the original occlusion of the SVG. After PCI for early SVG failure, 20.6% sustain an MI, and 30.6% of PCIs for late SVG failure are associated with MI (creatine kinase-myocardial band (CK-MB) greater than twice normal) <ref name="pmid15234406">{{cite journal |author=Caños DA, Mintz GS, Berzingi CO, Apple S, Kotani J, Pichard AD, Satler LF, Suddath WO, Waksman R, Lindsay J, Weissman NJ |title=Clinical, angiographic, and intravascular ultrasound characteristics of early saphenous vein graft failure |journal=Journal of the American College of Cardiology |volume=44 |issue=1 |pages=53–6 |year=2004 |month=July |pmid=15234406 |doi=10.1016/j.jacc.2004.03.045 |url=http://linkinghub.elsevier.com/retrieve/pii/S0735109704007132 |issn=}}</ref>. However, whether the MI preceded the intervention to treat SVG failure, or followed the intervention to treat SVG failure, SVG failure can reasonably be deemed to be the proximate cause of the event.
# One must be careful to '''distinguish between a) immediate peri-operative MIs during the index hospitalization, b) early MIs between the index hospitalization and a year, and c) late MIs (after a year'''). If one is evaluating a therapy targeted at reducing late atherothrombosis or drugs that reduce intimal hyperplasia, then events between b and c are most relevant. If one is investigating a therapy targeting thrombotic occlusion, then all periods (a,b, and c) are relevant.
# In observational studies, those patients who are alive to undergo repeat angiography are obviously included in the analyses, and those '''patients who died prior to angiography may not be included in the observational analysi'''s (i.e. there may not be imputation of an SVG failure to those patients who died). This results in underestimation of the association between SVG failure and mortality. For example, a report from the Duke Databank included those patients who survived to undergo subsequent cardiac catheterization, and excluded those patients who died by did not undergo cardiac catheterization <ref name="pmid16253593">{{cite journal |author=Halabi AR, Alexander JH, Shaw LK, Lorenz TJ, Liao L, Kong DF, Milano CA, Harrington RA, Smith PK |title=Relation of early saphenous vein graft failure to outcomes following coronary artery bypass surgery |journal=The American Journal of Cardiology |volume=96 |issue=9 |pages=1254–9 |year=2005 |month=November |pmid=16253593 |doi=10.1016/j.amjcard.2005.06.067 |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-9149(05)01266-X |issn=}}</ref>.
#The SVG may close and the native artery may remain open minimizing the symptoms associated with SVG failure. SVG failure may therefore by clinically "silent" or may not be closely associated with "hard endpoints" such as [[myocardial infarction]]([[MI]]).
#Despite the native artery remaining open after SVG failure, it should be realized that '''placement of an SVG is associated with more rapid disease progression in the grafted native coronary artery'''. SVG placement therefore exposes the patient to a risk of more rapid native disease progression. There is a 4 to 6 fold increase in the risk of proximal native vessel occlusion following the placement of an SVG, while there is limited impact upon disease progression downstream from the SVG <ref name="pmid18268427">{{cite journal | author = Borowski A, Vchivkov I, Ghodsizad A, Gams E | title = Coronary artery disease progression in patients who need repeat surgical revascularisation: the surgeon's point of view | journal = [[Journal of Cardiovascular Medicine (Hagerstown, Md.)]] | volume = 9 | issue = 1 | pages = 85–8 | year = 2008 | month = January | pmid = 18268427 | doi = 10.2459/JCM.0b013e328011439e | url = http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=1558-2027&volume=9&issue=1&spage=85 | issn = | accessdate = 2010-10-31}}</ref><ref name="pmid11292927">{{cite journal | author = Hamada Y, Kawachi K, Yamamoto T, Nakata T, Kashu Y, Watanabe Y, Sato M | title = Effect of coronary artery bypass grafting on native coronary artery stenosis. Comparison of internal thoracic artery and saphenous vein grafts | journal = [[The Journal of Cardiovascular Surgery]] | volume = 42 | issue = 2 | pages = 159–64 | year = 2001 | month = April | pmid = 11292927 | doi = | url = | issn = | accessdate = 2010-10-31}}</ref><ref name="pmid8869860">{{cite journal | author = Rupprecht HJ, Hamm C, Ischinger T, Dietz U, Reimers J, Meyer J | title = Angiographic follow-up results of a randomized study on angioplasty versus bypass surgery (GABI trial). GABI Study Group | journal = [[European Heart Journal]] | volume = 17 | issue = 8 | pages = 1192–8 | year = 1996 | month = August | pmid = 8869860 | doi = | url = http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=8869860 | issn = | accessdate = 2010-10-31}}</ref><ref name="pmid312703">{{cite journal | author = Guthaner DF, Robert EW, Alderman EL, Wexler L | title = Long-term serial angiographic studies after coronary artery bypass surgery | journal = [[Circulation]] | volume = 60 | issue = 2 | pages = 250–9 | year = 1979 | month = August | pmid = 312703 | doi = | url = http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=312703 | issn = | accessdate = 2010-10-31}}</ref> . While long-term studies demonstrate that as many as 22/23 grafted vessels occlude proximal to the SVG insertion site, the patency beyond the SVG insertion remains better (only 8 of 39 segments failed)<ref name="pmid312703">{{cite journal | author = Guthaner DF, Robert EW, Alderman EL, Wexler L | title = Long-term serial angiographic studies after coronary artery bypass surgery | journal = [[Circulation]] | volume = 60 | issue = 2 | pages = 250–9 | year = 1979 | month = August | pmid = 312703 | doi = | url = http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=312703 | issn = | accessdate = 2010-10-31}}</ref>. Progression of native disease is more rapid in segments bypassed by and SVG than those bypassed by an arterial conduit (p = 0.001, odds ratio = 2.03)<ref name="pmid9800822">{{cite journal | author = Manninen HI, Jaakkola P, Suhonen M, Rehnberg S, Vuorenniemi R, Matsi PJ | title = Angiographic predictors of graft patency and disease progression after coronary artery bypass grafting with arterial and venous grafts | journal = [[The Annals of Thoracic Surgery]] | volume = 66 | issue = 4 | pages = 1289–94 | year = 1998 | month = October | pmid = 9800822 | doi = | url = http://linkinghub.elsevier.com/retrieve/pii/S0003-4975(98)00757-7 | issn = | accessdate = 2010-10-31}}</ref>. In summary, if the SVG fails, the patient most often is left with greater progression of the underlying native vessel disease than they would have had had they not had an SVG placed. It is difficult to ascertain the impact of native vessel disease acceleration given the limited duration of follow-up in trials of SVGs. The impact of disease progression may not be apparent for many years and may be underestimated in current trials and analyses.
#As a nuance of the above, '''the impact of SVG failure may depend in part upon when it occurs'''.
#SVG failure not only leads to a potential reduction in antegrade blood flow to the bypassed segment as a result of vessel closure, '''there is also the potential for embolizaiton from a large occluded conduit into the downstream native circulation'''. SVGs do not have sidebranches and there is therefore no capacity for alternate run off when occlusion occurs. As a result, SVGs often occlude back to the origin of the SVG. Furthermore, the diameter of SVG often exceeds that of native arteries. As a result of the fact that the SVG occludes back to the ostium and is of a larger volume than a native coronary artery, there is a much larger embolic burden associated with a SVG.
#Consistent with the embolic hazard cited above, is the fact that dilation of an SVG failure does not lead to improved clinical outcomes. The fact that opening a closed SVG does not lead to improved outcomes may lead to inappropriate confusion surrounding SVG failure as a relevant clinical outcome. While it may be intuitive that opening an occluded or failed SVG would lead to improved outcomes (consistent with SVG failure being a surrogate), opening the occluded SVG may instead lead to embolizaiton of a large amount of the thrombotic material downstream. '''''Preventing SVG occlusion may be related to improved outcomes, but treating SVG occlusion after it occurs may not be related to improved outcomes.''''' The failure of reopening an occluded SVG to improve outcomes should not detract from the importance and relevance of preventing SVG occlusion in the first place as a valid surrogate endpoint.
#The patient is the unit of randomization, but failure of an SVG is the unit most closely related to clinical events.
# The impact of '''SVG failure must be interpreted in the context of the presence and patency of arterial conduits'''. The impact of SVG failure that includes failure of an SVG to the [[left anterior descending]] may be quite different than failure of an SVG to the RCA in the presence of a patent [[left internal mammary artery]].
#The impact of SVG failure must be interpreted in the context of the patency and disease status of the native vessel.
#The impact of SVG failure must be interpreted in the context of left ventricular function as well as associated co-morbidities (renal failure, diabetes and advanced age which are all associated with SVG failure).
#Is the timing of SVG failure relevant? '''If an anticoagulant (either [[antiplatelet]] or [[antithrombin]]) is undergoing evaluation of its efficacy in the prevention of thrombotic graft closure, then it is irrelevant if this thrombotic closure is early (in the immediate peri-operative period) or late'''. It could be hypothesized that the clinical benefit of the anticoagulant agent would be operative during both the early and late follow-up periods.
#'''Patients may not return for follow-up angiography and this may result in ascertainment bias.''' Maybe the patient is feeling so well they don't feel compelled to return for repeat angiography (you missed a positive treatment effect), or maybe they are so sick they can't show up (you missed a negative treatment effect). If patients died, traditionally they are counted or imputed as having SVG failure on both a per patient and a per SVG conduit basis. The percent of patients who returned for follow-up angiography was 80% in the PREVENT 4 study <ref name="pmid16287955">{{cite journal |author=Alexander JH, Hafley G, Harrington RA, Peterson ED, Ferguson TB, Lorenz TJ, Goyal A, Gibson M, Mack MJ, Gennevois D, Califf RM, Kouchoukos NT |title=Efficacy and safety of edifoligide, an E2F transcription factor decoy, for prevention of vein graft failure following coronary artery bypass graft surgery: PREVENT IV: a randomized controlled trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=294 |issue=19 |pages=2446–54 |year=2005 |month=November |pmid=16287955 |doi=10.1001/jama.294.19.2446 |url= |issn= |accessdate=2010-07-12}}</ref>
# The patient may return for follow-up angiography, but one or more of the SVGs cannot be engaged and selectively injected. As stated above, in the PREVENT 4 study, the use of saphenous vein graft markers improved the odds of finding SVGs in particular occluded SVGs <ref name="pmid18222256">{{cite journal | author = Olenchock SA, Karmpaliotis D, Gibson WJ, Murphy SA, Southard MC, Ciaglo L, Buros J, Mack MJ, Alexander JH, Harrington RA, Califf RM, Kouchoukos NT, Ferguson TB, Gibson CM | title = Impact of saphenous vein graft radiographic markers on clinical events and angiographic parameters | journal = [[The Annals of Thoracic Surgery]] | volume = 85 | issue = 2 | pages = 520–4 | year = 2008 | month = February | pmid = 18222256 | doi = 10.1016/j.athoracsur.2007.10.061 | url = http://linkinghub.elsevier.com/retrieve/pii/S0003-4975(07)02191-1 | issn = | accessdate = 2010-10-31}}</ref>. However, the SVG stenosis 70% or greater at follow-up did not differ by use of markers (25.8% with marker vs 24.4% without marker, p = not significant). In other words, there does not seem to be ascertainment bias whereby failure to find the SVG results in a different outcome (the outcomes in patients with SVG markers with a greater degree of ascertainment of the endpoint were no different).
#'''There are both per patient and per SVG units of analysis.''' Analyses should be presented on both a per patient basis (the unit of randomization) and a per SVG basis (the unit that is associated with clinical events). Because the behavior of multiple SVGs may be correlated, and this within patient correlation may reduce the estimate of the variance in the population, '''an adjustment for the within patient correlation must be provided when presenting the results on a per SVG basis'''<ref name="pmid8462141">{{cite journal | author = Gibson CM, Kuntz RE, Nobuyoshi M, Rosner B, Baim DS | title = Lesion-to-lesion independence of restenosis after treatment by conventional angioplasty, stenting, or directional atherectomy. Validation of lesion-based restenosis analysis | journal = [[Circulation]] | volume = 87 | issue = 4 | pages = 1123–9 | year = 1993 | month = April | pmid = 8462141 | doi = | url = http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=8462141 | issn = | accessdate = 2010-10-31}}</ref>. The within patient conocrdance can be adjusted for using a General Linear Model of Intraclass Correlation (GLIMIC) <ref name="pmid8462141">{{cite journal | author = Gibson CM, Kuntz RE, Nobuyoshi M, Rosner B, Baim DS | title = Lesion-to-lesion independence of restenosis after treatment by conventional angioplasty, stenting, or directional atherectomy. Validation of lesion-based restenosis analysis | journal = [[Circulation]] | volume = 87 | issue = 4 | pages = 1123–9 | year = 1993 | month = April | pmid = 8462141 | doi = | url = http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=8462141 | issn = | accessdate = 2010-10-31}}</ref>.

===Association of SVG Failure with Clinical Events===

There are multiple mechanisms whereby SVG patency is related to clinical outcomes:
#Closure of the conduit may reduce antegrade blood flow
#There may be embolization into the native vessel from the thrombosed SVG conduit, the diameter of which often exceeds the native coronary artery
#The SVG may have accelerate native vessel disease which predisposes the patient to adverse outcomes when the vessel occludes

Fitzgibbon and colleagues evaluated the clinical outcomes among 1,388 patients with 5,065 grafts over 25 years at a single center. SVG occlusion occurring 1 year after CABG was associated with reoperation and mortality <ref name="pmid8772748">{{cite journal |author=Fitzgibbon GM, Kafka HP, Leach AJ, Keon WJ, Hooper GD, Burton JR |title=Coronary bypass graft fate and patient outcome: angiographic follow-up of 5,065 grafts related to survival and reoperation in 1,388 patients during 25 years |journal=Journal of the American College of Cardiology |volume=28 |issue=3 |pages=616–26 |year=1996 |month=September |pmid=8772748 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/0735-1097(96)00206-9 |issn=}}</ref>.

In the PREVENT 4 study, the rate of death or MI outside the immediate perioperative period was 13.9% among patients with SVG failure and 0.9% among those without SVG failure <ref name="pmid16287955">{{cite journal |author=Alexander JH, Hafley G, Harrington RA, Peterson ED, Ferguson TB, Lorenz TJ, Goyal A, Gibson M, Mack MJ, Gennevois D, Califf RM, Kouchoukos NT |title=Efficacy and safety of edifoligide, an E2F transcription factor decoy, for prevention of vein graft failure following coronary artery bypass graft surgery: PREVENT IV: a randomized controlled trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=294 |issue=19 |pages=2446–54 |year=2005 |month=November |pmid=16287955 |doi=10.1001/jama.294.19.2446 |url= |issn= |accessdate=2010-07-12}}</ref>. The rate of immediate perioperative MI among patients with SVG failure was 13.4 and 6.8% among those patients without SVG failure.

===Association of SVG Failure after Stenting with Clinical Events===

The impact of SVG failure on clinical outcomes after SVG stenting was demonstrated among 80 patients with 112 lesions in the SOS (Stenting Of Saphenous Vein Grafts) Trial <ref name="pmid19778774">{{cite journal |author=Lichtenwalter C, de Lemos JA, Roesle M, Obel O, Holper EM, Haagen D, Saeed B, Iturbe JM, Shunk K, Bissett JK, Sachdeva R, Voudris VV, Karyofillis P, Kar B, Rossen J, Fasseas P, Berger P, Banerjee S, Brilakis ES |title=Clinical presentation and angiographic characteristics of saphenous vein graft failure after stenting: insights from the SOS (stenting of saphenous vein grafts) trial |journal=JACC. Cardiovascular Interventions |volume=2 |issue=9 |pages=855–60 |year=2009 |month=September |pmid=19778774 |doi=10.1016/j.jcin.2009.06.014 |url=http://linkinghub.elsevier.com/retrieve/pii/S1936-8798(09)00472-5 |issn=}}</ref>. Compared with BMS, DES (specifically paclitaxel elution) was associated with a reduced risk of SVG failure. SVG failure after stenting was associated with an [[acute coronary syndrome]] in 10 of the 24 patients (42%) . 7 of the 24 (29%) of patients presented with a [[non–ST-segment elevation acute myocardial infarction]]). Stable angina was present in 9 (37%) of SVG failure patients, and there were no symptoms in 5 (21%) SVG failure patients. The authors concluded that SVG failure after stenting presents as an acute myocardial infarction in 7/24 (30%) of cases. It is quite clear that SVG failure in an SVG that has had a stent placed is associated with worse clinical outcomes, and by extension, it stands to reason that SVG failure may be associated with worse clinical outcomes as well.

===Pathophysiologic Basis as to Why SVG Failure is Associated with Adverse Outcomes===
[[Image:Reasons why svg failure is bad.gif|thumb|600px|none]]

===Association of Primary PCI of Acutely Occluded SVGs with Adverse Events===

In several studies, if an SVG is the culprit vessel in acute MI, mortality is quite high <ref name="pmid12745114">{{cite journal |author=Nguyen TT, O'Neill WW, Grines CL, Stone GW, Brodie BR, Cox DA, Grines LL, Boura JA, Dixon SR |title=One-year survival in patients with acute myocardial infarction and a saphenous vein graft culprit treated with primary angioplasty |journal=The American Journal of Cardiology |volume=91 |issue=10 |pages=1250–4 |year=2003 |month=May |pmid=12745114 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0002914903002777 |issn=}}</ref>.

Indeed, some investigators have demonstrated that the mortality associated with SVG occlusion presenting as an MI and requiring intervention may be greater than that of native vessels <ref name="pmid11526358">{{cite journal |author=Al Suwaidi J, Velianou JL, Berger PB, Mathew V, Garratt KN, Reeder GS, Grill DE, Holmes DR |title=Primary percutaneous coronary interventions in patients with acute myocardial infarction and prior coronary artery bypass grafting |journal=American Heart Journal |volume=142 |issue=3 |pages=452–9 |year=2001 |month=September |pmid=11526358 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0002870301701561 |issn=}}</ref>. In the Mayo experience, a total of 1,072 patients with acute MI underwent primary PCI without prior lytics between 1991 and 1997. A total of 128 patients had previously undergone CABG and 944 had not undergone CABG. Of the patients who had previously undergone CABG, the primary PCI was performed in the native vessel in 65, and in the SVG itself in 63. In a multivariate model adjusting for co-morbidities, primary PCI of an SVG was independently associated with adverse cardiac events (death/MI/Repeat revascularization) (relative risk 1.48 [95% confidence interval 1.07-2.03], P =.02), but a history of prior CABG itself was not (relative risk 1.22 [95% confidence interval 0.96-1.56], P =.11).

In another study, patients with a thombosed SVG were at very high risk of subsequent events including mortality. <ref> Abdul-rahman R. Abdel-karim, MD; Subhash Banerjee, MD; Emmanouil S. Brilakis, MD, PhD. Percutaneous Intervention of Acutely Occluded Saphenous Vein Grafts: Contemporary Techniques and Outcomes. J Invasive Cardiol. 2010;22(6):253-257. </ref>The acute and long-term outcomes among 34 consecutive patients who underwent PCI of 36 acutely occluded SVGs between 2003 and 2009 at one institution were evaluated. Although PCI of the SVG was successful in 81% of the patients, 39% of these patients sustained stent thrombosis. After a mean follow-up of 2.3 ± 1.9 years, the mortality at 1 year was 8% and the mortality at 3 years was 42%. An acute coronary syndrome occurred in 15% of patients at 1 year and in 41% of patients at 3 years.

==References==
{{reflist|2}}

{{WH}}

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Interstitial lung disease (patient information)

2016-04-08T18:54:35Z

Sergekorjian:

{{Interstitial lung disease (patient information)}}
'''For the WikiDoc page for this topic, click [[Interstitial lung disease|here]]'''

{{CMG}};

==Overview==
Diffuse interstitial lung disease refers to a group of lung disorders in which the deep lung tissues become inflamed.

==What are the symptoms of Interstitial lung disease?==
Shortness of breath is a key symptom of interstitial lung disease. People may breathe faster or need to take deep breaths.

*At first, shortness of breath is not severe and you may only notice it with exercise, climbing stairs, and other hard activities.
*Over time, you may notice it while bathing or dressing, and then while eating or talking.
Most people with this condition also have a dry cough. A dry cough means you do not cough up any mucus or sputum.

Over time, weight loss, muscle and joint pain, and fatigue are also present.

People with advanced ILD may have:

*Abnormal enlargement of the base of the fingernails (clubbing).
*Blue color of the lips, skin, or fingernails due to low blood oxygen levels (cyanosis).

==What causes Interstitial lung disease?==
The lungs contain tiny air sacs (alveoli), which is where oxygen is absorbed. These air sacs open up or expand with each breath.

The tissue around these air sacs is called the interstitium. In people with interstitial lung disease, this tissue becomes stiff or scarred, and the air sacs are not able to expand as much. As a result, not as much oxygen can get into your lungs, and therefore to your body.

Interstitial lung diseases can be broken down into two large groups:

*Those that have no known cause (idiopathic ILD).
*Those with an identifiable cause or that occur along with other diseases.
There are several types of idiopathic ILD. Idiopathic pulmonary fibrosis (IPF) is the most common type. Less common types include:

*Acute interstitial pneumonitis (AIP).
*Cryptogenic organizing pneumonia or bronchiolitis obliterans organizing pneumonia (BOOP).
*Desquamative interstitial pneumonia (DIP).
*Lymphocytic interstitial pneumonia (LIP).
*Nonspecific interstitial pneumonitis (NSIP).
*Respiratory bronchiolitis interstitial lung disease (RBILD).
There are dozens of different causes of ILD.

*Autoimmune diseases (in which the immune system attacks the body) such as lupus, rheumatoid arthritis, sarcoidosis, and scleroderma.
*Certain infections.
*Certain medications (such as bleomycin, amiodarone, methotrexate, gold, infliximab, etanercept).
*Radiation therapy to the chest to treat breast cancer, lymphoma, and other cancers.
*Working with or around asbestos, coal dust, cotton dust, and silica dust.
Cigarette smoking may increase the risk of developing some forms of ILD and may cause the disease to be more severe.

==When to seek urgent medical care?==

*Your breathing is getting harder, faster, or more shallow than before.
*You cannot get a deep breath, or need to lean forward when sitting.
*You are having headaches more often.
*You feel sleepy or confused.
*You have a fever.
*You are coughing up dark mucus.
*Your fingertips or the skin around your fingernails is blue.

==Diagnosis==
The health care provider will perform a physical exam. Dry, crackling breath sounds may be heard when listening to the chest with a stethoscope. The health care provider may notice nasal flaring.

The following tests may be done:

*Blood tests to check for connective tissue diseases.
*Bronchoscopy with biopsy.
*Chest x-ray.
*CT scan of the chest.
*Lung biopsy.
*Measurement of the blood oxygen level at rest or during exertion.
*Pulmonary function tests.

==Treatment options==
Treatment depends on the cause of the disease. Anti-inflammatory drugs, such as corticosteroids or drugs that suppress the immune system, are prescribed if an autoimmune disease is causing the problem.

If there is no specific treatment for the condition, therapy is aimed at making you more comfortable and supporting lung function.

*If you smoke, ask the doctor or nurse about referring you to someone who can help you stop smoking.
*People with low blood oxygen levels will receive oxygen therapy in the home. A respiratory therapist will help you set up oxygen for use in the home or outside of the home. Families need to learn proper storage and safety, and how to keep an oxygen supply available.
*Lung rehabilitation can provide support, including teaching patients different breathing methods, how to set up the home to save energy, and how to eat enough calories and nutrients.
Some patients with advanced ILD may need a lung transplant.

==Where to find medical care for Interstitial lung disease?==
[http://maps.google.com/maps?q={{urlencode:{{#if:{{{1|}}}|{{{1}}}|map+top+hospital+Interstitial lung disease}}}}&oe=utf-8&rls=org.mozilla:en-US:official&client=firefox-a&um=1&ie=UTF-8&sa=N&hl=en&tab=wl Directions to Hospitals Treating Interstitial lung disease]

==What to expect (Outlook/Prognosis)?==
Chances of recovery or the disease getting worse depend on the cause, and how severe the disease was when it was first diagnosed.

==Possible complications==
*Pulmonary hypertension.
*Respiratory failure.
*Right-sided heart failure (cor pulmonale).
*When to Contact a Medical Professional.

==Prevention==
Avoid exposure to substances known to cause lung disease.

Quitting smoking can prevent ILD from getting worse.

People who are heavily exposed to known causes of occupational lung disease in the workplace are usually routinely screened for lung disease. These jobs can include coal miners, sand blasters, and ship workers.

==Sources==
http://www.nlm.nih.gov/medlineplus/ency/article/000128.htm
{{WH}}
{{WS}}

[[Category:Disease]]
[[Category:Pulmonology]]
[[Category:Pulmonary patient information]]
[[Category:Patient information]]
[[Category:Overview complete]]
[[Category:Template complete]]
[[Category:For review]]

Robust Sandwich Covariate Estimate

2016-03-28T12:11:18Z

Sergekorjian:

__NOTOC__
==Overview==
The '''Robust Sandwich Covariate Estimate''', also known as the Huber Sandwich Estimator and the Robust Sandwich Estimator, can be used to estimate the variance of an [[least squares|ordinary least squares]] (OLS) regression when the underlying model is incorrect, such as in the case of [[homoscedasticity]]. The Sandwich Estimator is generally only used when the OLE model has serious error and may benefit the variance, but the parameters being estimated by the OLE become meaningless to interpret <ref>Huber, P. J. (1967). “The Behavior of Maximum Likelihood Estimates under Nonstandard Conditions,” Proceedings of the Fifth Berkeley Symposium on Mathematical Statistics and Probability, vol. I, pp. 221–33.</ref>.

==When to use it?==
When trying to estimate standard error from data where [[heteroscedasticity]] is present (referring to the circumference in which the variability of a variable is unequal across the range of values of a second variable that it predicts). When estimating from heteroscedastic data, the ordinal least squares estimator will be consistent, but the estimated standard errors will be biased due to inequality in the dependent variables value across the independent variable.

==How does it work?==
For OLS, you can imagine that you're using the estimated variance of the residuals (under the assumption of independence and homoscedasticity) as an estimate for the conditional variance of the dependent variable. In the sandwich based estimator, you're using the observed squared residuals as a plug-in estimate of the same variance which can vary between observations. By using the square of the residuals, we get consistent estimates for the variance of the independent variables (the coefficients used in the model). These observed squared residuals will clean up any unexplained error due to heteroscedasticity that would otherwise been unexpected under the assumption of the constant covariance.

==References==
{{Reflist|2}}

Myelofibrosis medical therapy

2016-03-23T15:46:21Z

Sergekorjian: /* Treatment for Splenomegaly */

__NOTOC__
{{Myelofibrosis}}
{{CMG}}{{AE}}{{SR}}

==Overview==
Red blood cell transfusion, [[danazol]] therapy, or [[thalidomide]] are recommended for patients who develop anemia. [[Ruxolitinib]], an inhibitor of ''[[JAK1]]'' and ''[[JAK2]]'', can reduce the [[splenomegaly]] and the debilitating symptoms of [[weight loss]], [[fatigue]], and [[night sweats]] for patients with ''JAK2''-positive or ''JAK2''-negative primary myelofibrosis, post–essential thrombocythemia myelofibrosis, or post–polycythemia vera myelofibrosis.<ref name=treatmentoverviewofmyelofibrosis1>Treatment overview of primary myelofibrosis. National cancer institute 2016. http://www.cancer.gov/types/myeloproliferative/hp/chronic-treatment-pdq#section/_9. Accessed on March 10, 2016</ref> Hydroxyurea, [[chemotherapy]], [[radiotherapy]], or [[splenectomy]] are recommended for patients who develop splenomegaly.<ref name=treatmentoverviewofmyelofibrosis1>Treatment overview of primary myelofibrosis. National cancer institute 2016. http://www.cancer.gov/types/myeloproliferative/hp/chronic-treatment-pdq#section/_9. Accessed on March 10, 2016</ref>

==Medical Therapy==
Asymptomatic low-risk patients should be followed with a watchful waiting approach. Some individuals remain symptom-free for years. The development of [[anemia|symptomatic anemia]], [[leukocytosis|marked leukocytosis]], [[night sweats|drenching night sweats]], [[weight loss]], [[fever]], or [[splenomegaly|symptomatic splenomegaly]] would warrant therapeutic intervention.<ref name=treatmentoverviewofmyelofibrosis1>Treatment overview of primary myelofibrosis. National cancer institute 2016. http://www.cancer.gov/types/myeloproliferative/hp/chronic-treatment-pdq#section/_9. Accessed on March 10, 2016</ref>

===Treatment for Anemia===
*'''Red blood cell transfusion''':The profound [[anemia]] that develops in this disease usually requires red blood cell transfusion. Red blood cell survival is markedly decreased in some patients; this can sometimes be treated with glucocorticoids.<ref name=treatmentoverviewofmyelofibrosis1>Treatment overview of primary myelofibrosis. National cancer institute 2016. http://www.cancer.gov/types/myeloproliferative/hp/chronic-treatment-pdq#section/_9. Accessed on March 10, 2016</ref>
*'''Androgen therapy''': [[Danazol]] may stimulate the production of red blood cells and decrease the anemia.
*'''Erythropoietic growth factors''': [[Erythropoietin]] and [[darbepoetin]] are less likely to help when patients are transfusion dependent or manifest a serum erythropoietin level greater than 125 U/L.
*'''Thalidomide, lenalidomide, or pomalidomide''': These drugs may help in elevating the red blood cell counts, thus improving anemia, and reverse the splenomegaly. However, patients on thalidomide, lenalidomide, or pomalidomide require prophylaxis for avoiding thrombosis and careful monitoring for hematologic toxicity.<ref name=treatmentoverviewofmyelofibrosis1>Treatment overview of primary myelofibrosis. National cancer institute 2016. http://www.cancer.gov/types/myeloproliferative/hp/chronic-treatment-pdq#section/_9. Accessed on March 10, 2016</ref>

===''JAK2'' Inhibitor Therapy===
*[[Ruxolitinib]], an inhibitor of ''[[JAK1]]'' and ''[[JAK2]]'', can reduce the [[splenomegaly]] and the debilitating symptoms of [[weight loss]], [[fatigue]], and [[night sweats]] for patients with ''JAK2''-positive or ''JAK2''-negative primary myelofibrosis, post–essential thrombocythemia myelofibrosis, or post–polycythemia vera myelofibrosis.

===Treatment for Splenomegaly===
*'''''JAK2'' inhibitor therapy''': Painful splenomegaly can be treated temporarily with [[ruxolitinib]].
*'''Hydroxyurea''': Hydroxyurea can reduce the splenomegaly but may have a potential leukemogenic effect.
*'''Chemotherapy''': Drugs like [[thalidomide]], [[lenalidomide]], or [[cladribine]] may reduce the spleen size, and relieve the pain symptoms associated with it.
*'''Radiation therapy''': [[Radiation]] may be used to kill the cells and reduce the size of the spleen, when [[splenectomy]] is contraindicated.
*'''Splenectomy''': Surgical removal of the spleen.

==References==
{{reflist|2}}

[[Category:Disease]]
[[Category:Types of cancer]]
[[Category:Hematology]]
[[Category:Oncology]]

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Myelofibrosis risk factors

2016-03-23T15:26:26Z

Sergekorjian: /* Risk Factors */

__NOTOC__
{{Myelofibrosis}}
{{CMG}}{{AE}}{{SR}}

==Overview==
Common risk factors in the development of myelofibrosis may be age, [[myeloproliferative disorder|other myeloproliferative disorders]], [[radiation]], or industrial chemical exposure.<ref name=riskfactorsofmyelofibrosismayoclinic1>Risk factors for myelofibrosis. Mayo clinic 2016. http://www.mayoclinic.org/diseases-conditions/myelofibrosis/basics/risk-factors/con-20027210. Accessed on March 7, 2016</ref>

==Risk Factors==
Common risk factors for the development of myelofibrosis may include:<ref name=riskfactorsofmyelofibrosismayoclinic1>Risk factors for myelofibrosis. Mayo clinic 2016. http://www.mayoclinic.org/diseases-conditions/myelofibrosis/basics/risk-factors/con-20027210. Accessed on March 7, 2016</ref>
*'''Age''': Myelofibrosis most commonly affects individuals in their 50s and 60s.
*'''Other myeloproliferative disorder''': Myelofibrosis may also develop secondary to [[essential thrombocythemia]] or [[polycythemia vera]].
*'''Radiation exposure''': Individuals exposed to high levels of [[radiation]] (e.g. Thorotrast) have an increased risk of myelofibrosis.
*'''Chemicals''': Industrial chemicals, such as toluene and benzene, may have an increased risk of developing myelofibrosis.

==References==
{{reflist|2}}

[[Category:Oncology]]
[[Category:Disease]]
[[Category:Types of cancer]]
[[Category:Hematology]]

{{WH}}
{{WS}}

Myelofibrosis risk factors

2016-03-23T15:26:11Z

Sergekorjian: /* Risk Factors */

__NOTOC__
{{Myelofibrosis}}
{{CMG}}{{AE}}{{SR}}

==Overview==
Common risk factors in the development of myelofibrosis may be age, [[myeloproliferative disorder|other myeloproliferative disorders]], [[radiation]], or industrial chemical exposure.<ref name=riskfactorsofmyelofibrosismayoclinic1>Risk factors for myelofibrosis. Mayo clinic 2016. http://www.mayoclinic.org/diseases-conditions/myelofibrosis/basics/risk-factors/con-20027210. Accessed on March 7, 2016</ref>

==Risk Factors==
Common risk factors for the development of myelofibrosis may include:<ref name=riskfactorsofmyelofibrosismayoclinic1>Risk factors for myelofibrosis. Mayo clinic 2016. http://www.mayoclinic.org/diseases-conditions/myelofibrosis/basics/risk-factors/con-20027210. Accessed on March 7, 2016</ref>
*'''Age''': Myelofibrosis most commonly affects individuals in their 50s and 60s.
*'''Other myeloproliferative disorder''': Myelofibrosis may also develop secondary to [[essential thrombocythemia]] or [[polycythemia vera]].
*'''Radiation exposure''':Individuals exposed to high levels of [[radiation]] (e.g. Thorotrast) have an increased risk of myelofibrosis.
*'''Chemicals''': Industrial chemicals, such as toluene and benzene, may have an increased risk of developing myelofibrosis.

==References==
{{reflist|2}}

[[Category:Oncology]]
[[Category:Disease]]
[[Category:Types of cancer]]
[[Category:Hematology]]

{{WH}}
{{WS}}