Mononucleosis natural history
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Lakshmi Gopalakrishnan, M.B.B.S. [2]
Overview
Natural history
Intial Prodrome
- Following the invasion of B cells by EBV there is a resultant acute elevation of cytokines which forms the background for the initial manifestation of disease which lasts for a week or two.
Recovery
- Usually, the longer the infected person remains symptomatic, the more the infection weakens the person's immune system, and hence the longer time is required to recover.
Dormant infection
- After an initial prodrome, the fatigue of mononucleosis 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 virus do not show symptoms of the disease, but remain carriers of the disease. This is especially true in children, in whom infection seldom causes more than a very mild cold which often goes undiagnosed.
- This dormant feature combined with long (4 to 6 week) incubation period of the disease, makes epidemiological control of the disease impractical.
Reactivation
- Approximately 6% of patients with prior infection have reported relapse.
- 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.
- In case of a weak immune system, there is a possibility of EBV reactivation; consistent with the evidence of immune activation observed in patients with chronic fatigue syndrome.
Chronic infection
- The course of the disease can also be chronic with symptoms lasting for months or years. This variant of mononucleosis has been referred to as chronic EBV syndrome or chronic fatigue syndrome.
- Although the most recent medical studies have discounted the link between chronic EBV infection and chronic fatigue syndrome, some patients anecdotally report that chronic fatigue lasting for years after mononucleosis is part of a CFS.
- This confusion seems to lie in the nature of the link (note: any association does not prove or disprove causality) and possible misapprehension as to the syndromic nature of CFS. Also, some of this confusion may be attributed to the use of a new, broadened revision of the CFS research criteria, which has been criticised as overly inclusive.
- However, current studies suggest that there is an association between infectious mononucleosis and CFS [1]. Additionally, chronic fatigue states appear to occur in 10% of those who contract mononucleosis.[2]
- While chronic fatigue may rather be a common side effect of infectious mononucleosis, it should be noted that CFS is more than chronic fatigue, requiring at least four other symptoms, and a number of findings have been published which are not typical of EBV infection, although some complications may be shared. Additionally some CFS patients do not even describe fatigue as their worst problem.
- Majority of chronic post-infectious fatigue states 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.
Prognosis
- 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.[3]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, the virus can reactivate and cause vague physical symptoms (or may be subclinical), and during this phase the virus can spread to others.
- Similar reactivation or chronic subclinical viral activity in susceptible hosts may trigger multiple host autoimmune diseases, such as:
- Such chronic immunologic stimulation may also trigger multiple type of cancers, particularly lymphoma—strongest cancer associations with EBV are:
- EBV's potential to trigger such a wide range of autoimmune diseases and cancers probably relates to its primary infection of B lymphocytes (the primary antibody-producing cell of the immune system) and ability to alter both lymphocyte proliferation and lymphocyte antibody production.[3][4]
- Fatalities from mononucleosis are extremely rare in developed nations. Potential mortal complications include splenic rupture, bacterial superinfections, hepatic failure and the development of viral myocarditis.
Complications
Hematological
- Autoimmune hemolytic anemia
- Thrombocytopenia
- Granulocytopenia
- Splenic rupture which may occur without trauma, but impact to the spleen also adds as a contributing factor.
Neurological
- Cranial nerve palsies (Bell’s palsy)
- Encephalitis
Hepatology
- Hepatitis causing elevation of serum bilirubin (in approximately 40% of patients). In rare cases, death may result from severe hepatitis or splenic rupture.
Cardiology
Respiratory
- Airway obstruction (adenopathy)
Non-fatal compliactions
Uncommon, nonfatal complications exist, including various forms of CNS and hematological affection:
- CNS: Meningitis, encephalitis, hemiplegia and transverse myelitis. EBV infection has also been proposed as a risk factor for the development of multiple sclerosis (MS)[5], but this has not been affirmed.
- Hematologic: EBV can cause autoimmune hemolytic anemia (direct Coombs test is positive) and various cytopenias.
References
- ↑ Hickie I, Davenport T, Wakefield D, Vollmer-Conna U, Cameron B, Vernon SD, Reeves WC, Lloyd A; Dubbo Infection Outcomes Study Group. Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. BMJ. 2006 Sep 16;333(7568):575
- ↑ Hickie I, Davenport T, Wakefield D, Vollmer-Conna U, Cameron B, Vernon SD, Reeves WC, Lloyd A; Dubbo Infection Outcomes Study Group. Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. BMJ. 2006 Sep 16;333(7568):575
- ↑ Sitki-Green D, Covington M, Raab-Traub N (2003). "Compartmentalization and transmission of multiple epstein-barr virus strains in asymptomatic carriers". Journal of Virology. 77 (3): 1840–7. PMC 140987. PMID 12525618. Retrieved 2012-02-23. Unknown parameter
|month=ignored (help) - ↑ Hadinoto V, Shapiro M, Greenough TC, Sullivan JL, Luzuriaga K, Thorley-Lawson DA (2008). "On the dynamics of acute EBV infection and the pathogenesis of infectious mononucleosis". Blood. 111 (3): 1420–7. doi:10.1182/blood-2007-06-093278. PMC 2214734. PMID 17991806. Retrieved 2012-02-23. Unknown parameter
|month=ignored (help) - ↑ Ascherio A, Munger KL (2007). "Environmental risk factors for multiple sclerosis. Part I: the role of infection". Ann. Neurol. 61 (4): 288–99. doi:10.1002/ana.21117. PMID 17444504.