Infectious mononucleosis

Infectious mononucleosis (also known in North America as mono, the kissing disease or Pfeiffer's disease, and more commonly known as glandular fever in other English-speaking countries) is a disease seen most commonly in adolescents and young adults, characterized by fever, sore throat and fatigue. It is caused by the Epstein-Barr virus (EBV) or the cytomegalovirus (CMV). It is typically transmitted from asymptomatic individuals through saliva or blood, or by sharing a drinking glass, eating utensils, or needles. The disease is far less contagious than is commonly thought. Since the causative virus is also found in the mucus of the infected person, it could be contracted in the—albeit, highly unlikely—circumstance of ingesting droplets from a carrier's cough or sneeze.

It is estimated that 90% to 95% of adults in the world have EBV-antibodies, having been infected with the Epstein-Barr virus at some point in their lives. The vast majority of infections do not result in the development of mononucleosis. The virus infects B cells (B-lymphocytes), producing a reactive lymphocytosis and the atypical T cells (T-lymphocytes). Early childhood infections often cause no symptoms. In developed countries with less crowded conditions and better hygiene, children do not commonly become infected until adolescence. Since they also typically begin dating at that age, the co-occurrence of mono and kissing have led to its being called the "kissing disease," although this is but one of its modes of transmission.

The disease is so-named because the count of mononuclear leukocytes (white blood cells with a one-lobed nucleus) rises significantly. There are two main types of mononuclear leukocytes: monocytes and lymphocytes. They normally account for about 35% of all white blood cells. With Mono, it can become 50-70% Also, the total white blood count increases 10000-20000 per cubic millimeter.

Epidemiology

The incidence of clinically recognizable infectious mononucleosis caused by EBV is estimated at 45 per 100 000 in the US. In developing countries, an estimated 90% of children undergo an asymptomatic EBV-infection, and thus are not susceptible to infectious mononucleosis of EBV.

Clinical presentation

A person can be infected with the virus for weeks or months before any symptoms appear. Symptoms usually appear 4-7 weeks after infection, and may resemble strep throat or other bacterial or viral respiratory infections. These first signs of the disease are commonly confused with cold and flu symptoms. The typical symptoms and signs of mononucleosis are:

Fever - this varies from mild to severe, but is seen in nearly all cases.
Enlarged and tender lymph nodes - particularly the posterior cervical lymph nodes, on both sides of the neck.
Sore throat - seen in nearly all patients with EBV-mononucleosis
Fatigue (sometimes extreme fatigue)

Some patients also display:

Enlarged spleen (splenomegaly, which may lead to rupture) or liver (hepatomegaly)
Abdominal pain
Aching muscles
Headache
Loss of appetite
Jaundice
Depression
Weakness
Skin rash

After an initial prodrome of 1-2 weeks, the fatigue of mono often lasts from 1-2 months. The virus can remain dormant in the B cells indefinitely after symptoms have disappeared, and resurface at a later date. Many people exposed to the Epstein-Barr virus do not show symptoms of the disease, but carry the virus and can transmit it to others. This is especially true in children, in whom infection seldom causes more than a very mild illness which often goes undiagnosed. This feature, along with mono's long incubation period, makes epidemiological control of the disease impractical. About 6% of people who have had mono will relapse.

Mononucleosis can cause the spleen to swell, which in rare cases may lead to a ruptured spleen. Rupture may occur without trauma, but impact to the spleen is usually a factor. Other complications include hepatitis (inflammation of the liver) causing jaundice, and anemia (a deficiency of red blood cells). In rare cases, death may result from severe hepatitis or splenic rupture.

Reports of splenomegaly (enlarged spleen) in infectious mononucleosis suggest variable prevalence rates of 25% to 75%. Among pediatric patients, a splenomegaly rate of 50% is expected,with a rate of 60% reported in one case series.[2 Although splenic rupture is a rare complication of infectious mononucleosis, it is the basis of advice to avoid contact sports for 4-6 weeks after diagnosis.

Usually, the longer the infected person experiences the symptoms the more the infection weakens the person's immune system and the longer he/she will need to recover. Cyclical reactivation of the virus, although rare in healthy people, is often a sign of immunological abnormalities in the small subset of organic disease patients in which the virus is active or reactivated.

Although the great majority of cases of mononucleosis are caused by the E.B. virus, cytomegalovirus can produce a similar illness, usually with less throat pain. Due to the presence of the atypical lymphocytes on the blood smear in both conditions, most clinicians include both infections under the diagnosis of "mononucleosis." Symptoms similar to those of mononucleosis can be caused by adenovirus and the protozoan Toxoplasma gondii.

Atypical presentations of mononucleosis/EBV infection

In small children, the course of the disease is frequently asymptomatic. The course of the disease can also be chronic. Some patients suffer fever, tiredness, lassitude (abnormal fatigue), depression, lethargy, and chronic lymph node swelling, for months or years. This variant of mononucleosis is often referred to as chronic EBV syndrome or chronic fatigue syndrome. In case of a weakening of the immune system, a reactivation of the Epstein-Barr Virus is possible, though the course of the resultant disease is usually milder.

Laboratory tests

The laboratory hallmark of the disease is the presence of so-called atypical lymphocytes (a type of mononuclear cell, see image) on the peripheral blood smear. In addition, the overall white blood cell count is almost invariably increased, particularly the number of lymphocytes. The mono spot tests for infectious mononucleosis by examining the patient's blood for so-called heterophile antibodies, which cause agglutination (sticking together) of non-human red blood cells. This screening test is non-specific. Confirmation of the exact etiology can be obtained through tests to detect antibodies to the causative viruses. The mono spot test may be negative in the first week, so negative tests are often repeated at a later date. Since the mono spot test is usually negative in children less than 6-8 years old, an EBV serology test should be done on them if mononucleosis is suspected.

An older test is the Paul Bunnell test, in which the patient's serum is mixed with sheep red blood cells. If EBV is present, antibodies will usually be present that cause the sheep's blood cells to agglutinate. This test has been replaced by the mono spot and more specific EBV and CMV antibody tests.

Treatment

Infectious mononucleosis is generally self-limiting and only symptomatic and/or supportive treatments are used.Beers MH, Porter RS, Jones TV, Kaplan JL, Berkwits M, editors. The Merck manual of diagnosis and therapy. 18th ed. Whitehouse Station (NJ): Merck Research Laboratories; 2006. ISBN 0-911910-18-2 Rest is recommended during the acute phase of the infection, but activity should be resumed once acute symptoms have resolved. Nevertheless heavy physical activity and contact sports should be avoided to avoid the risk of splenic rupture, for at least one month following initial infection and until splenomegaly has resolved, as determined by ultrasound scan.Beers MH, Porter RS, Jones TV, Kaplan JL, Berkwits M, editors. The Merck manual of diagnosis and therapy. Whitehouse Station (NJ): Merck Research Laboratories; 2006. ISBN 0-911910-18-2

In terms of pharmacotherapies, paracetamol (acetaminophen) or non-steroidal anti-inflammatory drugs (NSAIDs) may be used to reduce fever and pain – aspirin is not used due to the risk of Reye's syndrome in children and young adults. Intravenous corticosteroids, usually hydrocortisone or dexamethasone, are not routinely used but may be useful if there is a risk of airways obstruction, severe thrombocytopenia, or hemolytic anemia.Antibiotic Expert Group. Therapeutic guidelines: Antibiotic. 13th ed. North Melbourne: Therapeutic Guidelines; 2006.Healthwise Inc. Infectious Mononucleosis. New York: WebMD; c1995–2006 2006 Jan 24; cited 2006 Jul 10. Available from: http://www.webmd.com/hw/infection/hw168622.asp

There is little evidence to support the use of aciclovir, although it may reduce initial viral shedding.Torre D, Tambini R. Acyclovir for treatment of infectious mononucleosis: a meta-analysis. Scand J Infect Dis 1999;31(6):543-7. PMID 10680982 Antibiotics are not used, being ineffective against viral infections, with amoxicillin and ampicillin contraindicated (for other infections) during mononucleosis as their use can frequently precipitate a non-allergic rash. Opioid analgesics are also contraindicated due to risk of respiratory depression.

Mortality/morbidity

Fatalities from mononucleosis are very rare in developed nations. Potential mortal complications include splenic rupture, bacterial superinfections, hepatic failure and the development of viral myocarditis.

Uncommon, nonfatal complications are rarely seen, but include various forms of CNS and hematological affection.
- CNS: Meningitis, encephalitis, hemiplegia, Guillain-Barré syndrome and transverse myelitis. EBV infection has also been proposed as a risk factor for the development of multiple sclerosis (MS), but this has not been affirmed.
- Hematologic: EBV can cause autoimmune hemolytic anemia (direct Coombs test is positive) and various cytopenias.

References

External links

Virology | Infectious diseases | Viruses

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