Infectious mononucleosis

File:Main symptoms of Infectious mononucleosis.png|publisher=medicinenet.com|access-date=18 June 2013|date=7 September 2011|url-status=live|archive-url=https://web.archive.org/web/20130618184041/http://www.medicinenet.com/infectious_mononucleosis/article.htm|archive-date=18 June 2013}}]]

File:Mononucleosis.JPG pharyngitis in a person with infectious mononucleosis]]

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File:Rash of amoxicillin use during EBV infection.jpg

The signs and symptoms of infectious mononucleosis vary with age.

Before puberty, the disease typically only produces flu-like symptoms, if any at all.{{Cite journal |last1=Sumaya |first1=C. V. |last2=Ench |first2=Y. |date=June 1985 |title=Epstein-Barr virus infectious mononucleosis in children. I. Clinical and general laboratory findings |url=https://pubmed.ncbi.nlm.nih.gov/2987784/#:~:text=Children%20with%20infectious%20mononucleosis,%20in,been%20reported%20in%20adult%20patients. |journal=Pediatrics |volume=75 |issue=6 |pages=1003–1010 |doi=10.1542/peds.75.6.1003 |issn=0031-4005 |pmid=2987784}} When found, symptoms tend to be similar to those of common throat infections (mild pharyngitis, with or without tonsillitis).

In adolescence and young adulthood, the disease presents with a characteristic triad:{{cite book|last=Cohen|first=Jeffrey I.|title=Epstein-Barr Virus|year=2005|publisher=Horizon Scientific Press|isbn=978-1-904455-03-5|pages=35–42|chapter-url=https://books.google.com/books?id=TRO-wXto8hcC&q=epstein-barr+jeffrey+I.+cohen+abstract|editor=Robertson, Erle S.|access-date=18 June 2013|chapter=Clinical Aspects of Epstein-Barr Infection|url-status=live|archive-url=https://web.archive.org/web/20140224131627/http://books.google.com/books?id=TRO-wXto8hcC&printsec=frontcover#v=onepage&q=epstein-barr%20jeffrey%20I.%20cohen%20abstract&f=false|archive-date=24 February 2014}}

• Fever – usually lasting 14 days;{{cite book|last1=Cohen|first1=Jonathan|last2=Powderly|first2=William G.|last3=Opal|first3=Steven M.|title=Infectious Diseases|date=2016|publisher=Elsevier Health Sciences|isbn=978-0-7020-6338-1|page=79|url=https://books.google.com/books?id=Dhq3DAAAQBAJ&pg=PA79|language=en|url-status=live|archive-url=https://web.archive.org/web/20170911003200/https://books.google.com/books?id=Dhq3DAAAQBAJ&pg=PA79|archive-date=2017-09-11}} often mild.
• Sore throat – usually severe for 3–5 days, before resolving in the next 7–10 days.{{cite book|last1=Bennett|first1=John E.|last2=Dolin|first2=Raphael|last3=Blaser|first3=Martin J.|title=Principles and Practice of Infectious Diseases|date=2014|publisher=Elsevier Health Sciences|isbn=978-1-4557-4801-3|page=1760|url=https://books.google.com/books?id=BseNCgAAQBAJ&pg=PA1760|language=en|url-status=live|archive-url=https://web.archive.org/web/20170911003200/https://books.google.com/books?id=BseNCgAAQBAJ&pg=PA1760|archive-date=2017-09-11}}
• Swollen glands –  mobile; usually located around the back of the neck (posterior cervical lymph nodes) and sometimes throughout the body.{{cite journal |last1=Weiss |first1=LM|last2=O'Malley|first2=D|title=Benign lymphadenopathies|journal=Modern Pathology|volume=26 |issue=Supplement 1 |pages=S88–S96 |year=2013|pmid=23281438|doi=10.1038/modpathol.2012.176|doi-access=free}}

Another major symptom is feeling tired. Headaches are common, and abdominal pains with nausea or vomiting sometimes also occur. Symptoms most often disappear after about 2–4 weeks. However, fatigue and a general feeling of being unwell (malaise) may sometimes last for months. Fatigue lasts more than one month in an estimated 28% of cases.{{cite book|last1=Robertson|first1=Erle S.|title=Epstein-Barr Virus|date=2005|publisher=Horizon Scientific Press|isbn=978-1-904455-03-5|page=36|url=https://books.google.com/books?id=TRO-wXto8hcC&pg=PA36|language=en|url-status=live|archive-url=https://web.archive.org/web/20170911003200/https://books.google.com/books?id=TRO-wXto8hcC&pg=PA36|archive-date=2017-09-11}} Mild fever, swollen neck glands and body aches may also persist beyond 4 weeks.{{cite journal|last=Luzuriaga|first=K|author2=Sullivan, JL|title=Infectious mononucleosis|journal=The New England Journal of Medicine|date=May 27, 2010|volume=362|issue=21|pages=1993–2000|pmid=20505178|doi=10.1056/NEJMcp1001116}} Most people are able to resume their usual activities within 2–3 months.

The most prominent sign of the disease is often pharyngitis, which is frequently accompanied by enlarged tonsils with pus—an exudate similar to that seen in cases of strep throat. In about 50% of cases, small reddish-purple spots called petechiae can be seen on the roof of the mouth.{{cite journal | author = Ebell MH | title = Epstein-Barr virus infectious mononucleosis | journal = American Family Physician | volume = 70 | issue = 7 | pages = 1279–87 |date=November 2004| pmid = 15508538}} Palatal enanthem can also occur, but is relatively uncommon.

A small minority of people spontaneously present a rash, usually on the arms or trunk, which can be macular (morbilliform) or papular. Almost all people given amoxicillin or ampicillin eventually develop a generalized, itchy maculopapular rash, which however does not imply that the person will have adverse reactions to penicillins again in the future.{{cite book|last=Johannsen|first=EC|title=Mandell, Douglas, and Bennett's principles and practice of infectious disease|year=2009|publisher=Churchill Livingstone|location=Philadelphia|isbn=978-0-443-06839-3|edition=7th|author2=Kaye, KM|editor=Mandell, GL |editor2=Bennett, JE |editor3=Dolin, R|chapter=Epstein-Barr virus (infectious mononucleosis, Epstein-Barr virus-associated malignant disease, and other diseases)}} Occasional cases of erythema nodosum and erythema multiforme have been reported. Seizures may also occasionally occur.{{cite book|last1=Shorvon|first1=Simon D.|last2=Andermann|first2=Frederick|last3=Guerrini|first3=Renzo|title=The Causes of Epilepsy: Common and Uncommon Causes in Adults and Children|date=2011|publisher=Cambridge University Press|isbn=978-1-139-49578-3|page=470|url=https://books.google.com/books?id=BUs-AYMBbC0C&pg=PA470|language=en|url-status=live|archive-url=https://web.archive.org/web/20180104013750/https://books.google.ca/books?id=BUs-AYMBbC0C&pg=PA470|archive-date=2018-01-04}}

Spleen enlargement is common in the second and third weeks, although this may not be apparent on physical examination. Rarely the spleen may rupture.{{cite web | title = Infectious Mononucleosis | date = 19 November 2019 | publisher = Johns Hopkins Medicine | url = https://www.hopkinsmedicine.org/health/conditions-and-diseases/infectious-mononucleosis | access-date = 23 Sep 2020}} There may also be some enlargement of the liver. Jaundice occurs only occasionally.{{cite journal|last1=Evans|first1=Alfred S.|title=Liver involvement in infectious mononucleosis|journal=Journal of Clinical Investigation|date=1 January 1948|volume=27|issue=1|pages=106–110|doi=10.1172/JCI101913|pmc=439479|pmid=16695521}}

It generally gets better on its own in people who are otherwise healthy. When caused by EBV, infectious mononucleosis is classified as one of the Epstein–Barr virus–associated lymphoproliferative diseases. Occasionally the disease may persist and result in a chronic infection. This may develop into systemic EBV-positive T cell lymphoma.{{cite journal | vauthors = Rezk SA, Zhao X, Weiss LM | title = Epstein-Barr virus (EBV)-associated lymphoid proliferations, a 2018 update | journal = Human Pathology | volume = 79 | pages = 18–41 | date = September 2018 | pmid = 29885408 | doi = 10.1016/j.humpath.2018.05.020 | s2cid = 47010934 }}

Infectious mononucleosis mainly affects younger adults. When older adults do catch the disease, they less often have characteristic signs and symptoms such as the sore throat and lymphadenopathy. Instead, they may primarily experience prolonged fever, fatigue, malaise and body pains. They are more likely to have liver enlargement and jaundice. People over 40 years of age are more likely to develop serious illness.

The exact length of time between infection and symptoms is unclear. A review of the literature made an estimate of 33–49 days.{{cite journal|last=Richardson|first=M|author2=Elliman, D |author3=Maguire, H |author4=Simpson, J |author5= Nicoll, A |title=Evidence base of incubation periods, periods of infectiousness and exclusion policies for the control of communicable diseases in schools and preschools|journal=The Pediatric Infectious Disease Journal|date=April 2001|volume=20|issue=4|pages=380–91|pmid=11332662|doi=10.1097/00006454-200104000-00004|s2cid=7700827}} In adolescents and young adults, symptoms are thought to appear around 4–6 weeks after initial infection.{{cite book |last=Cohen|first=Jeffrey I.| veditors=Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J |title=Harrison's principles of internal medicine |pages=380–91|publisher=McGraw-Hill Medical Publishing Division |location=New York |year=2008 |edition=17th |chapter=Epstein-Barr Infections, Including Infectious Mononucleosis|isbn=978-0-07-146633-2}} Onset is often gradual, though it can be abrupt.{{cite journal | vauthors = Odumade OA, Hogquist KA, Balfour HH | title = Progress and problems in understanding and managing primary Epstein-Barr virus infections | journal = Clin. Microbiol. Rev. | volume = 24 | issue = 1 | pages = 193–209 | date = January 2011 | pmid = 21233512 | pmc = 3021204 | doi = 10.1128/CMR.00044-10 }} The main symptoms may be preceded by 1–2 weeks of fatigue, feeling unwell and body aches.

{{Main|Epstein–Barr virus}}

About 90% of cases of infectious mononucleosis are caused by the Epstein–Barr virus, a member of the Herpesviridae family of DNA viruses. It is one of the most commonly found viruses throughout the world. Contrary to common belief, the Epstein–Barr virus is not highly contagious. It can only be contracted through direct contact with an infected person's saliva, such as through kissing or sharing toothbrushes.[http://www.mayoclinic.com/health/mononucleosis/AN00661 Mononucleosis and Epstein-Barr: What's the connection?] {{webarchive|url=https://web.archive.org/web/20130606232054/http://www.mayoclinic.com/health/mononucleosis/AN00661 |date=2013-06-06 }}. MayoClinic.com (2011-11-22). Retrieved on 2013-08-03. About 95% of the population has been exposed to this virus by the age of 40, but only 15–20% of teenagers and about 40% of exposed adults actually develop infectious mononucleosis.Schonbeck, John and Frey, Rebecca. The Gale Encyclopedia of Medicine. Vol. 2. 4th ed. Detroit: Gale, 2011. Online.

{{Main|Human betaherpesvirus 5}}

About 5–7% of cases of infectious mononucleosis is caused by human cytomegalovirus (CMV), another type of herpes virus.{{cite journal | vauthors=De Paor M, O'Brien K, Smith SM | title=Antiviral agents for infectious mononucleosis (glandular fever) | journal=The Cochrane Database of Systematic Reviews | volume=2016 | issue=12 | pages=CD011487 | year=2016 | doi = 10.1002/14651858.CD011487.pub2 | pmc=6463965 | pmid=27933614}} This virus is found in body fluids including saliva, urine, blood, tears,Larsen, Laura. Sexually Transmitted Diseases Sourcebook. Health Reference Series Detroit: Omnigraphics, Inc., 2009. Online. breast milk and genital secretions. A person becomes infected with this virus by direct contact with infected body fluids. Cytomegalovirus is most commonly transmitted through kissing and sexual intercourse. It can also be transferred from an infected mother to her unborn child. This virus is often "silent" because the signs and symptoms cannot be felt by the person infected. However, it can cause life-threatening illness in infants, people with HIV, transplant recipients, and those with weak immune systems. For those with weak immune systems, cytomegalovirus can cause more serious illnesses such as pneumonia and inflammations of the retina, esophagus, liver, large intestine, and brain. Approximately 90% of the human population has been infected with cytomegalovirus by the time they reach adulthood, but most are unaware of the infection.Carson-DeWitt and Teresa G. The Gale Encyclopedia of Medicine. Vol. 2. 3rd ed. Detroit: Gale, 2006. Once a person becomes infected with cytomegalovirus, the virus stays in their body throughout the person's lifetime. During this latent phase, the virus can be detected only in monocytes.{{cite journal |last1=Forte |first1=Eleonora |last2=Zhang |first2=Zheng |last3=Thorp |first3=Edward B. |last4=Hummel |first4=Mary |title=Cytomegalovirus Latency and Reactivation: An Intricate Interplay With the Host Immune Response |journal=Frontiers in Cellular and Infection Microbiology |date=31 March 2020 |volume=10 |page=130 |doi=10.3389/fcimb.2020.00130|doi-access=free|pmid=32296651 |pmc=7136410 }}

Toxoplasma gondii, a parasitic protozoon, is responsible for less than 1% of the infectious mononucleosis cases. Viral hepatitis, adenovirus, rubella, and herpes simplex viruses have also been reported as rare causes of infectious mononucleosis.{{cite journal |last1=Evans |first1=AS |title=Infectious mononucleosis and related syndromes. |journal=The American Journal of the Medical Sciences |date=November 1978 |volume=276 |issue=3 |pages=325–39 |doi=10.1097/00000441-197811000-00010 |pmid=217270|s2cid=22970983 }}

Epstein–Barr virus infection is spread via saliva, and has an incubation period of four to seven weeks.{{cite journal |author=Cozad J |title=Infectious mononucleosis |journal=The Nurse Practitioner |volume=21 |issue=3 |pages=14–6, 23, 27–8 |date=March 1996 |pmid=8710247 |doi=10.1097/00006205-199603000-00002 |s2cid=11827600 }} The length of time that an individual remains contagious is unclear, but the chances of passing the illness to someone else may be the highest during the first six weeks following infection. Some studies indicate that a person can spread the infection for many months, possibly up to a year and a half.{{cite web |url=http://kidshealth.org/WillisKnighton/en/teens/mono-long.html |title=How Long Is Mono Contagious? |publisher=Kidshealth.org |access-date=2016-11-19 |author=Elana Pearl Ben-Joseph |url-status=live |archive-url=https://web.archive.org/web/20161119181853/http://kidshealth.org/WillisKnighton/en/teens/mono-long.html |archive-date=2016-11-19 }} Date reviewed: January 2013

The virus replicates first within epithelial cells in the pharynx (which causes pharyngitis, or sore throat), and later primarily within B cells (which are invaded via their CD21). The host immune response involves cytotoxic (CD8-positive) T cells against infected B lymphocytes, resulting in enlarged, reactive lymphocytes (Downey cells).{{eMedicine|ped|705}}

When the infection is acute (recent onset, instead of chronic), heterophile antibodies are produced.

Cytomegalovirus, adenovirus and Toxoplasma gondii (toxoplasmosis) infections can cause symptoms similar to infectious mononucleosis, but a heterophile antibody test will test negative and differentiate those infections from infectious mononucleosis.{{cite web |url=http://www.gorhams.dk/html/the_lymphatic_system.html |title=The Lymphatic System |publisher=Lymphangiomatosis & Gorham's disease Alliance |access-date=2010-02-08 |url-status=dead |archive-url=https://web.archive.org/web/20100128094840/http://www.gorhams.dk/html/the_lymphatic_system.html |archive-date=2010-01-28 }}

Mononucleosis is sometimes accompanied by secondary cold agglutinin disease, an autoimmune disease in which abnormal circulating antibodies directed against red blood cells can lead to a form of autoimmune hemolytic anemia. The cold agglutinin detected is of anti-i specificity.{{cite book |author1=Ghosh, Amit K. |author2=Habermann, Thomas |title=Mayo Clinic Internal Medicine Concise Textbook |publisher=Informa Healthcare |year=2007 |isbn=978-1-4200-6749-1 }}{{Cite journal |author= Rosenfield RE |author2=Schmidt PJ |author3=Calvo RC |author4=McGinniss MH |title= Anti-i, a frequent cold agglutinin in infectious mononucleosis |journal= Vox Sanguinis |volume= 10 |issue= 5 |pages= 631–634 |doi= 10.1111/j.1423-0410.1965.tb01418.x |pmid= 5864820 |year= 1965|s2cid=30926697 }}

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The disease is diagnosed based on:

The presence of an enlarged spleen, and swollen posterior cervical, axillary, and inguinal lymph nodes 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. A physical examination may also show petechiae in the palate.

{{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 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). About 90% of diagnosed people have heterophile antibodies by week 3, disappearing in under a year. The antibodies involved in the test do not interact with the Epstein–Barr virus or any of its antigens.

The monospot test is not recommended for general use by the CDC due to its poor accuracy.

Serologic tests detect 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.

:*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.

• 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.

• 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.

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.{{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}}

• Elevated hepatic transaminase levels are highly suggestive of infectious mononucleosis, occurring in up to 50% of people.
• By blood film, one diagnostic criterion for infectious mononucleosis is the presence of 50% lymphocytes with at least 10% reactive lymphocytes (large, irregular nuclei),{{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 }} while the person also has fever, pharyngitis, and swollen lymph nodes. The reactive lymphocytes resembled monocytes when they were first discovered, thus the term "mononucleosis" was coined.
• A fibrin ring granuloma may be present in the liver or bone marrow.{{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 }}{{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 }}

About 10% of people who present a clinical picture of infectious mononucleosis do not have an acute Epstein–Barr-virus infection.{{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}} A differential diagnosis of acute infectious mononucleosis needs to take into consideration 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.

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.

People with infectious mononucleosis are sometimes misdiagnosed with a streptococcal pharyngitis (because of the symptoms of fever, pharyngitis and adenopathy) and are given antibiotics such as ampicillin or amoxicillin as treatment.{{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}}

Other conditions from which to distinguish infectious mononucleosis include leukemia, tonsillitis, diphtheria, common cold and influenza (flu).

Infectious mononucleosis is generally self-limiting, so only symptomatic or supportive treatments are used.{{cite book |veditors=Beers MH, Porter RS, Jones TV, Kaplan JL, Berkwits M |title=The Merck manual of diagnosis and therapy |edition=18th |publisher=Merck Research Laboratories |location=Whitehouse Station (NJ) |year=2006 |isbn=978-0-911910-18-6 |author=Mark H. Beers ... |url-access=registration |url=https://archive.org/details/merckmanual18the00mark }} The need for rest and return to usual activities after the acute phase of the infection may reasonably be based on the person's general energy levels. Nevertheless, in an effort to decrease the risk of splenic rupture, experts advise avoidance of contact sports and other heavy physical activity, especially when involving increased abdominal pressure or the Valsalva maneuver (as in rowing or weight training), for at least the first 3–4 weeks of illness or until enlargement of the spleen has resolved, as determined by a treating physician.{{cite journal|last=Putukian|first=M|author2=O'Connor, FG|author3=Stricker, P|author4=McGrew, C|author5=Hosey, RG|author6=Gordon, SM|author7=Kinderknecht, J|author8=Kriss, V|author9=Landry, G|title=Mononucleosis and athletic participation: an evidence-based subject review|journal=Clinical Journal of Sport Medicine|date=July 2008|volume=18|issue=4|pages=309–15|pmid=18614881|url=http://fammed.washington.edu/network/sfm/MonoReviewJuly2008%5B1%5D.pdf|access-date=18 June 2013|doi=10.1097/JSM.0b013e31817e34f8|s2cid=23780443|url-status=dead|archive-url=https://web.archive.org/web/20130923025409/http://fammed.washington.edu/network/sfm/MonoReviewJuly2008%5B1%5D.pdf|archive-date=23 September 2013}}

Paracetamol (acetaminophen) and NSAIDs, such as ibuprofen, may be used to reduce fever and pain. Prednisone, a corticosteroid, while used to try to reduce throat pain or enlarged tonsils, remains controversial due to the lack of evidence that it is effective and the potential for side effects.National Center for Emergency Medicine Informatics - Mononucleosis {{cite web |url=http://www.ncemi.org/cse/cse0314.htm |title=Mononucleosis (Glandular Fever) |access-date=2009-09-11 |url-status=dead |archive-url=https://web.archive.org/web/20090515154323/http://www.ncemi.org/cse/cse0314.htm |archive-date=2009-05-15 }}{{Cite journal|last1=Rezk|first1=Emtithal|last2=Nofal|first2=Yazan H.|last3=Hamzeh|first3=Ammar|last4=Aboujaib|first4=Muhammed F.|last5=AlKheder|first5=Mohammad A.|last6=Al Hammad|first6=Muhammad F.|date=2015-11-08|title=Steroids for symptom control in infectious mononucleosis|journal=The Cochrane Database of Systematic Reviews|volume=2015 |issue=11|pages=CD004402|doi=10.1002/14651858.CD004402.pub3|issn=1469-493X|pmid=26558642|pmc=7047551}} Intravenous corticosteroids, usually hydrocortisone or dexamethasone, are not recommended for routine use but may be useful if there is a risk of airway obstruction, a very low platelet count, or hemolytic anemia.{{cite web |title=Infectious Mononucleosis |url=http://www.webmd.com/hw/infection/hw168622.asp |date=January 24, 2006 |website=WebMD |access-date=2006-07-10 |url-status=live |archive-url=https://web.archive.org/web/20060706024151/http://www.webmd.com/hw/infection/hw168622.asp |archive-date=July 6, 2006 }}Antibiotic Expert Group. Therapeutic guidelines: Antibiotic. 13th ed. North Melbourne: Therapeutic Guidelines; 2006.

Antiviral agents act by inhibiting viral DNA replication. There is little evidence to support the use of antivirals such as aciclovir and valacyclovir although they may reduce initial viral shedding.{{cite journal |author=Torre D, Tambini R |title=Acyclovir for treatment of infectious mononucleosis: a meta-analysis |journal=Scand. J. Infect. Dis. |volume=31 |issue=6 |pages=543–47 |year=1999 |pmid=10680982 |doi=10.1080/00365549950164409|last2=Tambini }}{{cite journal|last1=De Paor|first1=M|last2=O'Brien|first2=K|last3=Fahey|first3=T|last4=Smith|first4=SM|title=Antiviral agents for infectious mononucleosis (glandular fever).|journal=The Cochrane Database of Systematic Reviews|date=8 December 2016|volume=2016|issue=12|pages=CD011487|pmid=27933614|doi=10.1002/14651858.CD011487.pub2|pmc=6463965}} Antivirals are expensive, risk causing resistance to antiviral agents, and (in 1% to 10% of cases) can cause unpleasant side effects. Although antivirals are not recommended for people with simple infectious mononucleosis, they may be useful (in conjunction with steroids) in the management of severe EBV manifestations, such as EBV meningitis, peripheral neuritis, hepatitis, or hematologic complications.{{cite journal |vauthors=Rafailidis PI, Mavros MN, Kapaskelis A, Falagas ME |title=Antiviral treatment for severe EBV infections in apparently immunocompetent patients |journal=J. Clin. Virol. |volume=49 |issue=3 |pages=151–57 |year=2010 |pmid=20739216 |doi=10.1016/j.jcv.2010.07.008 }}

Although antibiotics exert no antiviral action they may be indicated to treat bacterial secondary infections of the throat,{{cite web | title = Glandular fever - NHS | url = http://www.nhs.uk/Conditions/Glandular-fever/Pages/Introduction.aspx | publisher = National Health Service (NHS) | date = 2010-09-09 | access-date = 2010-09-09 | url-status=live | archive-url = https://web.archive.org/web/20100908234618/http://www.nhs.uk/conditions/glandular-fever/pages/introduction.aspx | archive-date = 2010-09-08 }} such as with streptococcus (strep throat). However, ampicillin and amoxicillin are not recommended during acute Epstein–Barr virus infection as a diffuse rash may develop.{{cite book|last1=Tyring|first1=Stephen|last2=Moore|first2=Angela Yen|last3=Lupi|first3=Omar|title=Mucocutaneous Manifestations of Viral Diseases: An Illustrated Guide to Diagnosis and Management|date=2016|publisher=CRC Press|isbn=978-1-4200-7313-3|page=125|edition=2|url=https://books.google.com/books?id=uAjLBQAAQBAJ&pg=PA125|language=en|url-status=live|archive-url=https://web.archive.org/web/20170911003200/https://books.google.com/books?id=uAjLBQAAQBAJ&pg=PA125|archive-date=2017-09-11}}

Splenomegaly is a common symptom of infectious mononucleosis and health care providers may consider using abdominal ultrasonography to get insight into the enlargement of a person's spleen.{{Citation |vauthors = ((American Medical Society for Sports Medicine))|date = 24 April 2014 |title = Five Things Physicians and Patients Should Question |publisher = American Medical Society for Sports Medicine |work = Choosing Wisely: an initiative of the ABIM Foundation |url = http://www.choosingwisely.org/doctor-patient-lists/american-medical-society-for-sports-medicine/ |access-date = 29 July 2014 |url-status=live |archive-url = https://web.archive.org/web/20140729224526/http://www.choosingwisely.org/doctor-patient-lists/american-medical-society-for-sports-medicine/ |archive-date = 29 July 2014 }}, which cites

• {{cite journal|last1=Putukian|first1=M|last2=O'Connor|first2=FG|last3=Stricker|first3=P|last4=McGrew|first4=C|last5=Hosey|first5=RG|last6=Gordon|first6=SM|last7=Kinderknecht|first7=J|last8=Kriss|first8=V|last9=Landry|first9=G|title=Mononucleosis and athletic participation: an evidence-based subject review|journal=Clinical Journal of Sport Medicine|date=Jul 2008|volume=18|issue=4|pages=309–15|pmid=18614881|doi=10.1097/JSM.0b013e31817e34f8|s2cid=23780443}}
• {{cite journal|last1=Spielmann|first1=AL|last2=DeLong|first2=DM|last3=Kliewer|first3=MA|title=Sonographic evaluation of spleen size in tall healthy athletes.|journal=AJR. American Journal of Roentgenology|date=Jan 2005|volume=184|issue=1|pages=45–9|pmid=15615949|doi=10.2214/ajr.184.1.01840045}} However, because spleen size varies greatly, ultrasonography is not a valid technique for assessing spleen enlargement and should not be used in typical circumstances or to make routine decisions about fitness for playing sports.

Serious complications are uncommon, occurring in less than 5% of cases:{{cite journal |author = Jensen, Hal B |date=June 2000 |title = Acute complications of Epstein-Barr virus infectious mononucleosis |journal = Current Opinion in Pediatrics |volume = 12 |issue = 3 |pages = 263–268 |issn = 1040-8703 |pmid = 10836164 |doi = 10.1097/00008480-200006000-00016 |s2cid=20566820 }}{{cite journal |author = Aghenta A |date=May 2008 |title = Symptomatic atrial fibrillation with infectious mononucleosis |journal = Canadian Family Physician |volume = 54 |issue = 5 |pages = 695–696 |pmc = 2377232 |pmid = 18474702 |last2 = Osowo |first2 = A |last3 = Thomas |first3 = J}}

• CNS complications include meningitis, encephalitis, hemiplegia, Guillain–Barré syndrome, and transverse myelitis. Prior infectious mononucleosis has been linked to the development of multiple sclerosis.{{cite journal | vauthors = Handel AE, Williamson AJ, Disanto G, Handunnetthi L, Giovannoni G, Ramagopalan SV | title = An updated meta-analysis of risk of multiple sclerosis following infectious mononucleosis | journal = PLOS ONE | volume = 5 | issue = 9 | pages = e12496| date = September 2010 | pmid = 20824132 | pmc = 2931696 | doi = 10.1371/journal.pone.0012496 | bibcode = 2010PLoSO...512496H | doi-access = free }}
• Hematologic: Hemolytic anemia (direct Coombs test is positive) and various cytopenias, and bleeding (caused by thrombocytopenia) can occur.
• Mild jaundice
• Hepatitis with the Epstein–Barr virus is rare.
• Upper airway obstruction from tonsillar hypertrophy is rare.
• Fulminant disease course of immunocompromised people are rare.
• Splenic rupture is rare.
• Myocarditis and pericarditis are rare.
• Postural orthostatic tachycardia syndrome
• Myalgic encephalomyelitis/chronic fatigue syndrome
• Cancers associated with the Epstein–Barr virus include Burkitt's lymphoma, Hodgkin's lymphoma and lymphomas in general as well as nasopharyngeal and gastric carcinoma.{{Cite journal|title = The role of Epstein-Barr virus in cancer.|date = November 2006|journal = Expert Opinion on Biological Therapy|last1 = Pattle|first1 = SB|pmid = 17049016|doi = 10.1517/14712598.6.11.1193|last2 = Farrell|first2 = PJ|volume=6|issue=11|pages=1193–205|s2cid = 36546018}}
• Hemophagocytic lymphohistiocytosis{{cite journal | vauthors = Marsh RA | title = Epstein–Barr Virus and Hemophagocytic Lymphohistiocytosis | journal = Frontiers in Immunology | volume = 8 | pages = 1902 | date = 2017 | pmid = 29358936 | pmc = 5766650 | doi = 10.3389/fimmu.2017.01902 | doi-access = free }}

Once the acute symptoms of an initial infection disappear, they often do not return. But once infected, the person carries the virus for the rest of their life. The virus typically lives dormant in B lymphocytes. Independent infections of mononucleosis may be contracted multiple times, regardless of whether the person is already carrying the virus dormant. Periodically, the virus can reactivate, during which time the person is again infectious, but usually without any symptoms of illness. Usually, a person with IM has few, if any, further symptoms or problems from the latent B lymphocyte infection. However, in susceptible hosts under the appropriate environmental stressors, the virus can reactivate and cause vague physical symptoms (or may be subclinical), and during this phase, the virus can spread to others.{{cite journal |vauthors=Sitki-Green D, Covington M, Raab-Traub N |title= Compartmentalization and Transmission of Multiple Epstein-Barr Virus Strains in Asymptomatic Carriers |journal= Journal of Virology |date=February 2003 |volume= 77 |issue= 3 |pages= 1840–1847 |doi= 10.1128/JVI.77.3.1840-1847.2003 |pmid= 12525618 |pmc= 140987 }}{{cite journal |vauthors=Hadinoto V, Shapiro M, Greenough TC, Sullivan JL, Luzuriaga K, Thorley-Lawson DA |title= On the dynamics of acute EBV infection and the pathogenesis of infectious mononucleosis |journal= Blood |date= February 1, 2008 |volume= 111 |issue= 3|pages= 1420–1427|doi= 10.1182/blood-2007-06-093278 |pmid= 17991806 |pmc= 2214734 }}

{{Further|Epstein–Barr virus#History}}

The characteristic symptomatology of infectious mononucleosis does not appear to have been reported until the late nineteenth century.{{cite journal|last=Altschuler|first=EL|title=Antiquity of Epstein-Barr virus, Sjögren's syndrome, and Hodgkin's disease--historical concordance and discordance|journal=Journal of the National Cancer Institute|date=1 September 1999|volume=91|issue=17|pages=1512–3|doi=10.1093/jnci/91.17.1512A|pmid=10469761|doi-access=free}} In 1885, the renowned Russian pediatrician Nil Filatov reported an infectious process he called "idiopathic adenitis" exhibiting symptoms that correspond to infectious mononucleosis, and in 1889 a German balneologist and pediatrician, Emil Pfeiffer, independently reported similar cases (some of lesser severity) that tended to cluster in families, for which he coined the term Drüsenfieber ("glandular fever").Н. Филатов: Лекции об острых инфекционных болезнях у детей [N. Filatov: Lektsii ob ostrikh infeksionnîkh boleznyakh u dietei]. 2 volumes. Moscow, A. Lang, 1887.E. Pfeiffer: Drüsenfieber. Jahrbuch für Kinderheilkunde und physische Erziehung, Wien, 1889, 29: 257–264.

The word mononucleosis has several senses,{{Citation |author=Elsevier |author-link=Elsevier |title=Dorland's Illustrated Medical Dictionary |publisher=Elsevier |url=http://dorlands.com/ |postscript=. Headword "mononucleosis". |access-date=2015-06-28 |archive-date=2014-01-11 |archive-url=https://web.archive.org/web/20140111192614/http://dorlands.com/ |url-status=dead }} but today it usually is used in the sense of infectious mononucleosis, which is caused by EBV.

Around the 1920’s , infectious mononucleosis was not known and there were not many things to test whether people were infected or not. Before this there weren't many cases disclosed besides a few and one of these would take place in 1896. This outbreak infected an Ohio community which ended leaving them devastated. Epidemics seemed to keep reappearing here and there including an outbreak that happened in which 87 people were infected in the Falcon Islands. Some other outbreaks that occurred around this time would include some nurseries and boarding schools and also the U.S. Naval Base, Coronado, Calif,  where hundreds were infected by this virus.{{Cite web |title=History |url=https://achh.army.mil/history/book-wwii-communicablediseasesv5-chapter13/ |access-date=2024-10-28 |website=achh.army.mil |language=en}}

The term "infectious mononucleosis" was coined in 1920 by Thomas Peck Sprunt and Frank Alexander Evans in a classic clinical description of the disease published in the Bulletin of the Johns Hopkins Hospital, entitled "Mononuclear leukocytosis in reaction to acute infection (infectious mononucleosis)".{{cite journal|last=Evans|first=AS|title=The history of infectious mononucleosis|journal=The American Journal of the Medical Sciences|date=March 1974|volume=267|issue=3|pages=189–95|pmid=4363554|doi=10.1097/00000441-197403000-00006}}Sprunt TPV, Evans FA. Mononuclear leukocytosis in reaction to acute infection (infectious mononucleosis). Bulletin of the Johns Hopkins Hospital. Baltimore, 1920;31:410-417. A lab test for infectious mononucleosis was developed in 1931 by Yale School of Public Health Professor John Rodman Paul and Walls Willard Bunnell based on their discovery of heterophile antibodies in the sera of persons with the disease.{{Cite web|url=https://publichealth.yale.edu/about/background/history/timeline.aspx|title=Historical Timeline {{!}} Yale School of Public Health|website=publichealth.yale.edu|access-date=2019-01-04|archive-url=https://web.archive.org/web/20190619163739/https://publichealth.yale.edu/about/background/history/timeline.aspx|archive-date=2019-06-19|url-status=dead}} The Paul-Bunnell Test or PBT was later replaced by the heterophile antibody test.

The Epstein–Barr virus was first identified in Burkitt's lymphoma cells by Michael Anthony Epstein and Yvonne Barr at the University of Bristol in 1964.{{Cite journal |last1=Ambinder |first1=Richard F. |last2=Xian |first2=Rena R. |date=2024-04-19 |title=Sir Michael Anthony Epstein (1921–2024) |url=https://www.science.org/doi/10.1126/science.adp2961 |journal=Science |language=en |volume=384 |issue=6693 |pages=274 |doi=10.1126/science.adp2961 |pmid=38635698 |bibcode=2024Sci...384..274A |issn=0036-8075}} The link with infectious mononucleosis was uncovered in 1967 by Werner and Gertrude Henle at the Children's Hospital of Philadelphia, after a laboratory technician handling the virus contracted the disease: comparison of serum samples collected from the technician before and after the onset revealed development of antibodies to the virus.{{cite journal |doi= 10.1056/NEJMbkrev39523 |last= Miller |first= George |date= December 21, 2006 |title= Book Review: Epstein–Barr Virus |journal= New England Journal of Medicine |volume= 355 |issue= 25 |pages= 2708–2709 }}{{cite journal | vauthors = Henle G, Henle W, Diehl V | title = Relation of Burkitt's tumor-associated herpes-ytpe virus to infectious mononucleosis | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 59 | issue = 1 | pages = 94–101 | date = January 1968 | pmid = 5242134 | pmc = 286007 | doi = 10.1073/pnas.59.1.94| bibcode = 1968PNAS...59...94H | doi-access = free }}

Yale School of Public Health epidemiologist Alfred E. Evans confirmed through testing that mononucleosis was transmitted mainly through kissing, leading to it being referred to colloquially as "the kissing disease".{{Cite news|url=https://www.nytimes.com/1996/01/25/us/alfred-s-evans-78-expert-on-origins-of-mononucleosis.html|title=Alfred S. Evans, 78, Expert On Origins of Mononucleosis|last=Fountain|first=Henry|date=1996-01-25|work=The New York Times|access-date=2019-01-04|language=en-US|issn=0362-4331}}

{{Reflist}}

• {{Commons category-inline|Infectious mononucleosis}}

{{Medical condition classification and resources

| DiseasesDB = 4387

| ICD10 = {{ICD10|B|27}}

| ICD9 = {{ICD9|075}}

| ICDO =

| OMIM =

| Curlie = Health/Conditions_and_Diseases/Infectious_Diseases/Viral/Epstein-Barr_Virus/Infectious_Mononucleosis/

| MedlinePlus = 000591

| eMedicineSubj = emerg

| eMedicineTopic = 319

| eMedicine_mult = {{eMedicine2|med|1499}} {{eMedicine2|ped|705}}

| MeshID = D007244

}}

{{Viral diseases}}

{{Authority control}}

{{DEFAULTSORT:Infectious Mononucleosis}}

Category:Epstein–Barr virus–associated diseases

Category:Virus-related cutaneous conditions

Category:Cytomegalovirus-associated diseases

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Category:Medical triads