Mononucleosis overview

# Overview
Epstein-Barr virus, frequently referred to as EBV, is a member of the herpesvirus family and one of the most common human viruses.

# Pathophysiology
Epstein-Barr virus, frequently referred to as EBV, is a member of the herpesvirus family that targets oro-pharyngeal epithelium and B cells. Transmission of the EBV through the air or blood does not normally occur. The incubation period, or the time from infection to appearance of symptoms, ranges from 4 to 6 weeks. Persons with infectious mononucleosis may be able to spread the infection to others for a period of weeks. However, no special precautions or isolation procedures are recommended, since the virus is also found frequently in the saliva of healthy people. In fact, many healthy people can carry and spread the virus intermittently for life. These people are usually the primary reservoir for person-to-person transmission. For this reason, transmission of the virus is almost impossible to prevent.

# Epidemiology and Demographics
Majority of mononucleosis syndromes are caused by Epstein-Barr virus, and most people become infected with EBV sometime during their lives with an estimated 90%-95% of persons greater than 21 years of age demonstrating antibody to EBV. In the United States, the disease occurs most often among older children and young adults; however, in certain socioeconomically depressed areas the infection affects young children who remain asymptomatic. Additionally, the dormant feature combined with long (4 to 6 week) incubation period of the disease, makes epidemiological control of the disease impractical.

# Risk Factors
Majority of the population become infected with EBV at sometime during their lives with an estimated 90%-95% of adults demonstrating seropositivity by 21 years of age. Therefore, even individuals exposed to infected contacts have shown to be previously infected with EBV and hence are not at risk for the manifestation of mononucleosis. However, once infected, the patient carries the virus for the rest of their life with the virus typically residing dormantly in the B lymphocytes. Independent infections of mononucleosis may be contracted multiple times, regardless of whether the patient is already carrying the virus dormantly. Periodic reactivation of the virus may occur, during which time the patient is again infectious, but usually without any symptoms of illness. Therefore, in susceptible hosts under the appropriate environmental stressors, reactivation of the virus occurs to cause vague subclinical symptoms or remain mostly asymptomatic and diagnosed only by a positive serologic response. However, its imperative to note that during this phase the virus can spread to others.

# Causes
Epstein-Barr virus is ubiquitous across the globe and the strongest causative agent for the manifestation of infectious mononucleosis. Commonly, a person is first exposed to the virus during or after adolescence. Though once deemed "The Kissing Disease", recent research has shown that transmission of mononucleosis not only occurs from intimate contact with infected saliva, but also from contact with the airborne virus.
For more information on the virus, click here

# Differentiating Mononucleosis from other Diseases
Acute mononucleosis, acute cytomegalovirus infection and toxoplasma gondii infection have similar clinical presentations. In addition, since their management is much the same, it is not always helpful, or possible, to distinguish between infectious mononucleosis and cytomegalovirus infection. However, in pregnant women, it is imperative to differentiate mononucleosis from toxoplasmosis as toxo is associated with significant consequences in the fetus. Acute HIV infection can also mimic signs similar to those of infectious mononucleosis, and tests should be performed in pregnant women for the same reason as toxoplasmosis.

# Natural History, Complications and Prognosis
Fatalities from mononucleosis are extremely rare in developed nations. However, chronic sub-clinical infection may persist secondary to the dormant virus within the B cells. Reactivation of the virus may occur in susceptible hosts under the appropriate environmental stressors. Similar such reactivation or chronic sub-clinical viral activity in susceptible hosts may trigger multiple host autoimmune diseases and cancers secondary to virus predilection to B lymphocytes and its ability to alter both lymphocyte proliferation and lymphocyte antibody production.

# Diagnosis

## History and Symptoms
Symptoms of infectious mononucleosis are fever, sore throat, and swollen lymph glands. Sometimes, a splenomegaly or hepatomegaly may develop. Heart problems or involvement of the central nervous system occurs only rarely, and infectious mononucleosis is almost never fatal. There are no known associations between active EBV infection and problems during pregnancy, such as miscarriages or birth defects. Although the symptoms of infectious mononucleosis usually resolve in 1 or 2 months, EBV remains dormant or latent in a few cells in the throat and blood for the rest of the person's life. Periodically, the virus can reactivate and is commonly found in the saliva of infected persons. This reactivation usually occurs without symptoms of illness.

## Physical Examination
The classic initial presentation of mononucleosis include: fever, lymphadenopathy, pharyngitis, rash and/or periorbital oedema. Occasionally, patients infected with EBV may also display splenomegaly, with subsequent life-threatening complication of splenic rupture and/or hepatomegaly.

## Laboratory Findings
In most cases of infectious mononucleosis, the clinical diagnosis can be made from the characteristic triad of fever, pharyngitis, and lymphadenopathy lasting for 1 to 4 weeks.

## Other Imaging Findings
Direct and indirect evidence of persistent viral infection long after recovery from acute illness has been found in patients with chronic fatigue syndrome. This is possibly due to the activation of microglia during the acute infection phase in such individuals. Lumbar puncture, EEG, CT scan and/or MRI may help to evaluate such patients with presumable CNS involvement.

## Other Diagnostic Studies
Bilateral tender lymphadenopathy, particularly, the posterior posterior cervical lymph nodes are characteristic of mononucleosis. Therefore, lymph node biopsy if done may reveal atypical lymphocytosis.

# Treatment

## Medical Therapy
Infectious mononucleosis is generally self-limiting and only symptomatic and/or supportive treatments are used. However, severe tonsillar enlargement may cause life-threatening airway obstruction and therefore, close monitoring of such high-risk patients is essential. Glucocorticoids may be indicated in such cases of severe airway obstruction. Acyclovir has been tried as they decrease oropharyngeal viral shedding. Recently, valacyclovir has shown to lower or eliminate the presence of the Epstein-Barr virus in subjects afflicted with acute mononucleosis, leading to a significant decrease in the severity of symptoms.

## Surgery
Infectious mononucleosis is generally self-limiting and only symptomatic and/or supportive therapy may be required. However, in cases of life-threatening splenic rupture which may occur even without trauma, immediate surgery may be life-saving.

## Primary Prevention
Majority of mononucleosis syndromes are caused by Epstein-Barr virus, and most people become infected with EBV sometime during their lives with an estimated 90-95% population aged more than 21 years demonstrate antibody to EBV. The transmission of the virus requires intimate contact with the saliva of an infected person and rarely occurs via air or blood. Therefore, the most reasonable way to prevent mono is to avoid close contact with infected saliva.