Mononucleosis causes

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Associate Editor(s)-In-Chief: Lakshmi Gopalakrishnan, M.B.B.S. [3]

Overview

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.

Diseases associated with EBV

• Infectious states:

• Infectious mononucleosis
• Stevens-Johnson syndrome
• Hepatitis
• Herpes
• Histiocytic necrotizing lymphadenitis (also known as Kikuchi's disease)

• Cancers:

• Non-Hodgkin's lymphomas, including primary cerebral lymphoma
• Hodgkin's disease
• Hairy leukoplakia
• Nasopharyngeal carcinoma
• Smooth muscle tumors

• Immunocompromised/suppressed states:

• Common variable immunodeficiency (CVID)
• Post-transplant lymphoproliferative disorder
• Multiple Sclerosis (higher risk in patients infected as teenagers than as children)

EBV-associated cancers

• Once the acute symptoms of an initial infection disappear, they often do not return. But once infected, the patient carries the virus for the rest of their life. The virus typically lives dormantly in B lymphocytes. Independent infections of mononucleosis may be contracted multiple times, regardless of whether the patient is already carrying the virus dormantly.

• Periodically, the virus can reactivate, during which time the patient is again infectious, but usually without any symptoms of illness. Usually, a patient has few, if any, further symptoms or problems from the latent B lymphocyte infection. However, in susceptible hosts under the appropriate environmental stressors, reactivation of the virus is observed and known to cause vague subclinical symptoms or remain mostly asymptomatic and is diagnosed by positive serologic response. Additionally, its imperative to note that during this phase the virus can spread to others.

• Similar such reactivation or chronic sub-clinical viral activity in susceptible hosts may trigger multiple host autoimmune diseases and cancers secondary to EBV's predilection to B lymphocytes (the primary antibody-producing cell of the immune system) and its ability to alter both lymphocyte proliferation and lymphocyte antibody production.

• The strongest evidence linking EBV and cancer formation is found in Burkitt's lymphoma and nasopharyngeal carcinoma.

• It has been postulated to be a trigger for a subset of chronic fatigue syndrome patients as well as multiple sclerosis and other autoimmune diseases.

• Other B cell lymphomas arise in immunocompromised patients such as those with AIDS or who have undergone organ transplantation with associated immunosuppression (post-transplant lymphoproliferative disorder (PTLD).

• Smooth muscle tumors are also associated with the virus in malignant patients.

Burkitt's Lymphoma

• Burkitt's lymphoma is a type of Non-Hodgkin's lymphoma and is most common in the equatorial Africa.
• It is co-existent with the presence of malaria. Malarial infection is shown to reduce the immune surveillance of EBV immortalized B cells; thereby, allowing their proliferation which in turn increases the chance of a mutation to occur. Repeated such mutations lead to the escape of B cells from cell-cycle control and furthermore allow the cells to proliferate unchecked, resulting in the formation of Burkitt's lymphoma.
• Commonly affects the jaw bone, forming a huge tumor mass.
• Responds quickly to chemotherapy treatment, namely cyclophosphamide, but recurrence is common.

Nasopharyngeal carcinoma

• Nasopharyngeal carcinoma is a cancer found in the upper respiratory tract, most commonly in the nasopharynx, and is linked to the EBV virus.
• Occurs secondary to both genetic and environmental factors
• Predominantly prevalent in Southern China and Africa. It is much more common in people of Chinese ancestry (genetic), but is also linked to the Chinese diet of a high amount of smoked fish, which contain nitrosamines, well known carcinogens (environmental).

Chronic fatigue syndrome

• In the late 1980s and early 1990s, EBV became the favored explanation for chronic fatigue syndrome. It was noted that people with chronic exhaustion had EBV, although it was also noted EBV was present in almost everyone.

• In a four year study, the Centers for Disease Control and Prevention found that the virus did not adhere to Koch's Postulates and therefore had no definitive association between CFS and EBV but it is still being studied by researchers.

• Majority of the chronic post-infectious fatigue state appear not to be caused by a chronic viral infection, but be triggered by the acute infection.

• Direct and indirect evidence of persistent viral infection has been found in CFS, for example in muscle and via detection of an unusually low molecular weight RNase L enzyme, although the commonality and significance of such findings is disputed.
• Hickie et al, contend that mononucleosis appears to cause a hit and run injury to the brain in the early stages of the acute phase, thereby causing the chronic fatigue state. This would explain why in mononucleosis, fatigue very often lingers for months after the Epstein Barr Virus has been controlled by the immune system.
• However, it has also been noted in several (although altogether rare) cases that the only "symptom" displayed by a mononucleosis sufferer is elevated moods and higher energy levels, virtually the opposite of CFS and comparable to hypomania.

• Just how infectious mononucleosis changes the brain and causes fatigue (or lack thereof) in certain individuals remains to be seen. Such a mechanism may include activation of microglia in the brain of some individuals during the acute infection, thereby causing a slowly dissipating fatigue.

References

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