Infectious mononucleosis

Source: Wikipedia, the free encyclopedia.
"Mononucleosis" redirects here. For excessive monocyte counts more generally, see Monocytosis.
Not to be confused with Pfeiffer syndrome (a genetic disorder).
Infectious mononucleosis
Other namesGlandular fever, Pfeiffer's disease, Filatov's disease,
pain medications such as paracetamol (acetaminophen) and ibuprofen[2][4]
Frequency45 per 100,000 per year (U.S.)[5]

Infectious mononucleosis (IM, mono), also known as glandular fever, is an infection usually caused by the

splenic rupture may occur.[6]

While usually caused by the Epstein–Barr virus, also known as human herpesvirus 4, which is a member of the

monospot test is not recommended for general use due to poor accuracy.[10]

There is no

pain medications such as paracetamol (acetaminophen) and ibuprofen.[2][4]

Mononucleosis most commonly affects those between the ages of 15 and 24 years in the

developing world, people are more often infected in early childhood when there are fewer symptoms.[13] In those between 16 and 20 it is the cause of about 8% of sore throats.[9] About 45 out of 100,000 people develop infectious mono each year in the United States.[5] Nearly 95% of people have had an EBV infection by the time they are adults.[5] The disease occurs equally at all times of the year.[9] Mononucleosis was first described in the 1920s and is colloquially known as "the kissing disease".[14]

Signs and symptoms

Main symptoms of infectious mononucleosis[15]
Exudative pharyngitis
in a person with infectious mononucleosis
Cross reaction rash
Rash from using penicillin while infected with IM[16]
Maculopapular rash from amoxicillin use during EBV infection
Maculopapular rash from amoxicillin use during EBV infection

The

symptoms
of infectious mononucleosis vary with age.

Children

Before puberty, the disease typically only produces

flu-like symptoms, if any at all. When found, symptoms tend to be similar to those of common throat infections (mild pharyngitis, with or without tonsillitis).[16]

Adolescents and young adults

In adolescence and young adulthood, the disease presents with a characteristic triad:[17]

Another major symptom is

feeling tired.[2] Headaches are common, and abdominal pains with nausea or vomiting sometimes also occur.[17] Symptoms most often disappear after about 2–4 weeks.[2][21] However, fatigue and a general feeling of being unwell (malaise) may sometimes last for months.[16] Fatigue lasts more than one month in an estimated 28% of cases.[22] Mild fever, swollen neck glands and body aches may also persist beyond 4 weeks.[16][23][24] Most people are able to resume their usual activities within 2–3 months.[23]

The most prominent sign of the disease is often the

roof of the mouth.[24] Palatal enanthem can also occur, but is relatively uncommon.[16]

A small minority of people spontaneously present a

adverse reactions to penicillins again in the future.[16][21] Occasional cases of erythema nodosum and erythema multiforme have been reported.[16] Seizures may also occasionally occur.[25]

Complications

Spleen enlargement is common in the second and third weeks, although this may not be apparent on physical examination. Rarely the spleen may rupture.[26] There may also be some enlargement of the liver.[24] Jaundice occurs only occasionally.[16][27]

It generally gets better on its own in people who are otherwise healthy.[28] 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.[28]

Older adults

Infectious mononucleosis mainly affects younger adults.[16] When older adults do catch the disease, they less often have characteristic signs and symptoms such as the sore throat and lymphadenopathy.[16][24] Instead, they may primarily experience prolonged fever, fatigue, malaise and body pains.[16] They are more likely to have liver enlargement and jaundice.[24] People over 40 years of age are more likely to develop serious illness.[29] (See Prognosis.)

Incubation period

The exact length of time between infection and symptoms is unclear. A review of the literature made an estimate of 33–49 days.[30] In adolescents and young adults, symptoms are thought to appear around 4–6 weeks after initial infection.[16] Onset is often gradual, though it can be abrupt.[29] The main symptoms may be preceded by 1–2 weeks of fatigue, feeling unwell and body aches.[16]

Cause

Epstein–Barr virus

Main article: Epstein–Barr virus

About 90% of cases of infectious mononucleosis are caused by the

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.[31] 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.[32]

Cytomegalovirus

Main article: Human betaherpesvirus 5

About 5–7% of cases of infectious mononucleosis is caused by

monocytes.[35]

Other causes

herpes simplex viruses have also been reported as rare causes of infectious mononucleosis. [7]

Transmission

Epstein–Barr virus infection is spread via saliva, and has an incubation period of four to seven weeks.[37] 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.[38]

Pathophysiology

The virus replicates first within

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, atypical lymphocytes (Downey cells).[39]

When the infection is acute (recent onset, instead of

antibodies are produced.[24]

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.[2][40]

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.[41][42]

Diagnosis

Infectious mononucleosis, peripheral smear, high power showing reactive lymphocytes
Splenomegaly due to mononucleosis resulting in a subcapsular hematoma
Splenomegaly due to mononucleosis resulting in a subcapsular hematoma

The disease is diagnosed based on:

Physical examination

The presence of an

petechiae in the palate.[24]

Heterophile antibody test

Main article: 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

false-negative rate of as high as 25% in the first week, 5–10% in the second, and 5% in the third).[24] 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.[43]

The monospot test is not recommended for general use by the CDC due to its poor accuracy.[10]

Serology

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.[10]
  • 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.[10]
  • 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.[10]
  • 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.[10]

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.[44]

Other tests

Differential diagnosis

About 10% of people who present a clinical picture of infectious mononucleosis do not have an acute Epstein–Barr-virus infection.

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.[24]

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.[24]

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.[48]

Other conditions from which to distinguish infectious mononucleosis include leukemia, tonsillitis, diphtheria, common cold and influenza (flu).[43]

Treatment

Infectious mononucleosis is generally

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.[24][50]

Medications

tonsils, remains controversial due to the lack of evidence that it is effective and the potential for side effects.[51][52] 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.[53][54]

Antiviral agents act by inhibiting viral DNA replication.

valacyclovir although they may reduce initial viral shedding.[55][56] Antivirals are expensive, risk causing resistance to antiviral agents, and (in 1% to 10% of cases) can cause unpleasant side effects.[33] 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.[57]

Although antibiotics exert no antiviral action they may be indicated to treat bacterial

strep throat). However, ampicillin and amoxicillin are not recommended during acute Epstein–Barr virus infection as a diffuse rash may develop.[59]

Observation

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.[60] 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.[60]

Prognosis

Serious complications are uncommon, occurring in less than 5% of cases:[61][62]

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.[2] 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.[2][66][67]

History

Further information: Epstein–Barr virus § History

The characteristic symptomatology of infectious mononucleosis does not appear to have been reported until the late nineteenth century.

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").[69][70][71]

The word mononucleosis has several senses,[72] but today it usually is used in the sense of infectious mononucleosis, which is caused by EBV.

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)".[69][73] 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.[74] 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. 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.[75][76]

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".[77]

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External links
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