Editing Infectious mononucleosis (section)

==Diagnosis==
[[File:Infectious Mononucleosis 3.jpg|thumb|upright=1.3|Infectious mononucleosis, peripheral smear, high power showing reactive lymphocytes]]
[[File:SplenomegalyandsubcaphematomaCorMark.png|thumb|upright=1.3|Splenomegaly due to mononucleosis resulting in a subcapsular hematoma]]
[[File:SplenomegalyandsubcaphematomaMarked.png|thumb|upright=1.3|Splenomegaly due to mononucleosis resulting in a subcapsular hematoma]]

The disease is diagnosed based on:

===Physical examination===
The presence of an [[splenomegaly|enlarged spleen]], and swollen posterior [[cervical lymph nodes|cervical]], [[axillary lymph nodes|axillary]], and [[inguinal lymph node]]s are the most useful to suspect a diagnosis of infectious mononucleosis. On the other hand, the absence of swollen cervical lymph nodes and fatigue are the most useful to dismiss the idea of infectious mononucleosis as the correct diagnosis. The insensitivity of the physical examination in detecting an enlarged spleen means it should not be used as evidence against infectious mononucleosis.<ref name=Ebell2004/> A physical examination may also show [[petechiae]] in the [[palate]].<ref name=Ebell2004/>

===Heterophile antibody test===
{{Main|Heterophile antibody test}}
The heterophile antibody test, or monospot test, works by agglutination of red blood cells from guinea pigs, sheep and horses. This test is specific but not particularly [[sensitivity and specificity|sensitive]] (with a [[false-negative]] rate of as high as 25% in the first week, 5–10% in the second, and 5% in the third).<ref name=Ebell2004/> About 90% of diagnosed people have heterophile antibodies by week 3, disappearing in under a year. The [[antibody|antibodies]] involved in the test do not interact with the Epstein–Barr virus or any of its [[antigen]]s.<ref name=Longmore2007/>

The monospot test is not recommended for general use by the [[Centers for Disease Control and Prevention|CDC]] due to its poor accuracy.<ref name="CDC2014Diag"/>

===Serology===
Serologic tests detect [[antibody|antibodies]] directed against the Epstein–Barr virus. [[Immunoglobulin G]] (IgG), when positive, mainly reflects a past infection, whereas [[immunoglobulin M]] (IgM) mainly reflects a current infection. EBV-targeting antibodies can also be classified according to which part of the virus they bind to:
* Viral capsid antigen (VCA):
:*Anti-VCA IgM appear early after infection, and usually, disappear within 4 to 6 weeks.<ref name=CDC2014Diag/>
:*Anti-VCA IgG appears in the acute phase of EBV infection, reaches a maximum at 2 to 4 weeks after onset of symptoms and thereafter declines slightly and persists for the rest of a person’s life.<ref name=CDC2014Diag/>
* Early antigen (EA)
:*Anti-EA IgG appears in the acute phase of illness and disappears after 3 to 6 months. It is associated with having an active infection. Yet, 20% of people may have antibodies against EA for years despite having no other sign of infection.<ref name=CDC2014Diag/>
* EBV nuclear antigen (EBNA)
:*Antibody to EBNA slowly appears 2 to 4 months after the onset of symptoms and persists for the rest of a person’s life.<ref name=CDC2014Diag/>

When negative, these tests are more accurate than the heterophile antibody test in ruling out infectious mononucleosis. When positive, they feature similar specificity to the heterophile antibody test. Therefore, these tests are useful for diagnosing infectious mononucleosis in people with highly suggestive symptoms and a negative heterophile antibody test.<ref>{{Citation |last1=Stuempfig |first1=Nathan D. |title=Monospot Test |date=2023 |url=http://www.ncbi.nlm.nih.gov/books/NBK539739/ |work=StatPearls |access-date=2023-06-15 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30969561 |last2=Seroy |first2=Justin |archive-date=2024-04-06 |archive-url=https://web.archive.org/web/20240406064025/https://www.ncbi.nlm.nih.gov/books/NBK539739/ |url-status=live }}</ref>

===Other tests===
* Elevated hepatic [[transaminase]] levels are highly suggestive of infectious mononucleosis, occurring in up to 50% of people.<ref name=Ebell2004/>
* By [[blood film]], one diagnostic criterion for infectious mononucleosis is the presence of 50% [[lymphocyte]]s with at least 10% [[reactive lymphocyte]]s (large, irregular [[cell nucleus|nuclei]]),<ref name=Longmore2007>{{cite book | last=Longmore | first=Murray |author2=Ian Wilkinson |author3=Tom Turmezei |author4=Chee Kay Cheung  | title=Oxford Handbook of Clinical Medicine, 7th edition | publisher=Oxford University Press | year=2007 | page=389 | isbn=978-0-19-856837-7 }}</ref> while the person also has fever, pharyngitis, and [[lymphadenopathy|swollen lymph nodes]]. The reactive lymphocytes resembled [[monocyte]]s when they were first discovered, thus the term "mononucleosis" was coined.
* A [[fibrin ring granuloma]] may be present in the liver or bone marrow.<ref>{{cite journal |last1=Ruel |first1=M. |last2=Sevestre |first2=H. |last3=Henry-Biabaud |first3=E. |last4=Courouce |first4=A. M. |last5=Capron |first5=J. P. |last6=Erlinger |first6=S. |title=Fibrin ring granulomas in hepatitis A |journal=Digestive Diseases and Sciences |date=December 1992 |volume=37 |issue=12 |pages=1915–1917 |doi=10.1007/BF01308088|pmid=1473440 |s2cid=25008261 }}</ref><ref>{{cite journal |last1=Chung |first1=Hee-Jung |last2=Chi |first2=Hyun-Sook |last3=Jang |first3=Seongsoo |last4=Park |first4=Chan-Jeoung |title=Epstein-Barr Virus Infection Associated With Bone Marrow Fibrin-Ring Granuloma |journal=American Journal of Clinical Pathology |date=1 February 2010 |volume=133 |issue=2 |pages=300–304 |doi=10.1309/AJCPB7SX7QXASPSK|pmid=20093240 }}</ref>

===Differential diagnosis===
About 10% of people who present a clinical picture of infectious mononucleosis do not have an acute Epstein–Barr-virus infection.<ref name=Bravender2010>{{cite journal|last=Bravender|first=T|title=Epstein-Barr virus, cytomegalovirus, and infectious mononucleosis|journal=Adolescent Medicine: State of the Art Reviews|date=August 2010|volume=21|issue=2|pages=251–64, ix|pmid=21047028}}</ref> A differential diagnosis of acute infectious mononucleosis needs to take into consideration [[Human cytomegalovirus|acute cytomegalovirus infection]] and ''[[Toxoplasma gondii]]'' infections. Because their management is much the same, it is not always helpful–or possible–to distinguish between Epstein–Barr-virus mononucleosis and cytomegalovirus infection. However, in pregnant women, differentiation of mononucleosis from [[toxoplasmosis]] is important, since it is associated with significant consequences for the [[fetus]].<ref name=Ebell2004/>

Acute [[HIV infection]] can mimic signs similar to those of infectious mononucleosis, and tests should be performed for pregnant women for the same reason as toxoplasmosis.<ref name=Ebell2004/>

People with infectious mononucleosis are sometimes misdiagnosed with a [[streptococcal pharyngitis]] (because of the symptoms of fever, [[pharyngitis]] and [[Lymphadenopathy|adenopathy]]) and are given antibiotics such as [[ampicillin]] or [[amoxicillin]] as treatment.<ref>{{cite web|url= https://www.lecturio.com/concepts/mononucleosis/|title= Mononucleosis|website= The Lecturio Medical Concept Library|date= 4 August 2020|access-date= 11 August 2021|archive-date= 11 August 2021|archive-url= https://web.archive.org/web/20210811080259/https://www.lecturio.com/concepts/mononucleosis/|url-status= live}}</ref>

Other conditions from which to distinguish infectious mononucleosis include [[leukemia]], [[tonsillitis]], [[diphtheria]], [[common cold]] and [[influenza]] (flu).<ref name=Longmore2007/>