Infectious mononucleosis
| Infectious mononucleosis | |
 | |
|---|---|
| Infectious Mononucleosis smear showing reactive (atypical) lymphocytes, in blue. | |
| ICD-10 | B27 |
| ICD-9 | 075 |
| DiseasesDB | 4387 |
| MedlinePlus | 000591 |
| eMedicine | emerg/319 med/1499 ped/705 |
| MeSH | D007244 |
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Infectious mononucleosis, (also known as the kissing disease, or Pfeiffer's disease, in North America as mono and more commonly known as glandular fever in other English-speaking countries) is seen most commonly in adolescents and young adults, characterized in teenagers by fever, sore throat, muscle soreness, and fatigue. Mononucleosis typically produces a very mild illness in small children. White patches on the tonsils or in the back of the throat may also be seen (resembling strep throat). Mononucleosis is usually caused by the Epstein-Barr virus (EBV), which infects B cells (B-lymphocytes), producing a reactive lymphocytosis and atypical T cells (T-lymphocytes) known as Downey bodies.
Mononucleosis is typically transmitted from asymptomatic individuals through saliva (hence "the kissing disease"), or by sharing a drink, or sharing eating utensils. It may also be transmitted through blood. The disease is far less contagious than is commonly thought. In rare cases a person may have a high resistance to infection.
The disease is so-named because the count of mononuclear leucocytes (white blood cells with a one-lobed nucleus) rises significantly. There are two main types of mononuclear leucocytes: monocytes and lymphocytes. They normally account for about 35% of all white blood cells. With infectious mononucleosis, this can rise to 50-70%. Also, the total white blood count may increase to 10,000-20,000 per cubic millimeter.
Symptoms
Symptoms usually appear 1-2 months after infection, and may resemble strep throat, or other bacterial or viral respiratory infections. The typical symptoms and signs of mononucleosis are:
- Fever—this varies from mild to severe, but is seen in nearly all cases.
- Tender and enlarged/swollen lymph nodes—particularly the posterior cervical lymph nodes, on both sides of the neck.
- Sore throat—White patches on the tonsils and back of the throat are often seen
- Fatigue (sometimes extreme fatigue)
Some patients also display:
- Enlarged spleen (splenomegaly, which may lead to rupture) and/or liver (hepatomegaly)
- Petechial hemorrhage
- Abdominal pain
- Aching muscles
- Headache
- Loss of appetite
- Jaundice
- Depression
- Weakness
- Skin rash
- Dizziness or disorientation
- Uncontrolled shaking at times
- Dry cough
- Enlarged Prostate
- Supra-orbital oedema—the eyes become puffy and swollen—may occur in the early stages of infection
After an initial prodrome of 1-2 weeks, the fatigue of infectious 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 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 (4 to 6 week) incubation period, makes epidemiological control of the disease impractical. About 6% of people who have had infectious mononucleosis will relapse.
Mononucleosis can cause the spleen to swell. Rupture may occur without trauma, but impact to the spleen is also a factor. Other complications include hepatitis (inflammation of the liver) causing elevation of serum bilirubin (in approximately 40% of patients), jaundice (approximately 5% of cases), 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,[1] 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 all 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, some physicians confusingly used to include both infections under the diagnosis of "mononucleosis," though EBV is by definition the infection that must be present for this illness. Symptoms similar to those of mononucleosis can be caused by adenovirus, acute HIV infection 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 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 (CFS). In case of a weakening of the immune system, a reactivation of the Epstein-Barr Virus is possible; in CFS there is evidence of immune activation also.
Although studies conducted by the CDC and others have discounted a link between EBV and CFS, some patients anecdotally report that chronic fatigue lasting for years after mono 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. Current studies suggest there is an association between infectious mononucleosis and CFS [1]. "Chronic fatigue states" appear to occur in 10% of those who contract mononucleosis[2] Some confusion here may be due to the use of a new, broadened revision of the CFS research criteria, which has been criticised as overly inclusive. Although chronic fatigue may then be a rather 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 (see "Mortality/morbidity" below). Additionally some CFS patients do not describe fatigue as their worst problem.
Perhaps a 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
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.
Mononucleosis causes so-called heterophile antibodies, which cause agglutination (sticking together) of non-human red blood cells, to appear in the patient's blood. The monospot is a non-specific test that screens for mononucleosis by looking for these antibodies. Confirmation of the exact etiology can be obtained through tests to detect specific antibodies to the causative viruses. The spot test may be negative in the first week, so negative tests are often repeated at a later date. Since the 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 for heterophile antibodies is the Paul-Bunnell test, in which the patient's serum is mixed with sheep red blood cells and checked for agglutination of these cells.
Treatment
Infectious mononucleosis is generally self-limiting and only symptomatic and/or supportive treatments are used.[3] 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 abrogate the risk of splenic rupture, for at least one month following initial infection and until splenomegaly has resolved, as determined by ultrasound scan.[3]
In terms of pharmacotherapies, acetaminophen/paracetamol 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 recommended for routine use[4] but may be useful if there is a risk of airway obstruction, severe thrombocytopenia, or hemolytic anemia.[5][6]
There is little evidence to support the use of aciclovir, although it may reduce initial viral shedding.[7] However, the antiviral drug valacyclovir has recently been 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.[8][9][10] 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. In a small percentage of cases, mononucleosis infection is complicated by co-infection with streptococcal infection in the throat and tonsils (strep throat). Penicillin or other antibiotics should be administered to treat the strep throat, but are not effective against EBV. Opioid analgesics are also contraindicated due to risk of respiratory depression.[5]
Mortality/morbidity
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.
Uncommon, nonfatal complications exist, including various forms of CNS and hematological affection.
- CNS: Meningitis, encephalitis, hemiplegia and transverse myelitis. EBV infection has also been propsed as a risk factor for the development of multiple sclerosis (MS)[11], 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
- ↑ 3.0 3.1 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
- ↑ Candy B, Hotopf M. (2006). "Steroids for symptom control in infectious mononucleosis". Cochrane Database Sys Rev (4): CD004402. doi:10.1002/14651858.CD004402.pub2.
- ↑ 5.0 5.1 Antibiotic Expert Group. Therapeutic guidelines: Antibiotic. 13th ed. North Melbourne: Therapeutic Guidelines; 2006.
- ↑ Healthwise Inc. Infectious Mononucleosis. New York: WebMD; c1995–2006 [updated 2006 Jan 24; cited 2006 Jul 10]. Available from: http://www.webmd.com/hw/infection/hw168622.asp
- ↑ Torre D, Tambini R. Acyclovir for treatment of infectious mononucleosis: a meta-analysis. Scand J Infect Dis 1999;31(6):543-7. PMID 10680982
- ↑ Balfour et al. (December 2005) A controlled trial of valacyclovir in infectious mononucleosis. Presented at the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC., December 18, 2005. Abstract V1392
- ↑ Simon et al. (March 2003) The Effect of Valacyclovir and Prednisolone in Reducing Symptoms of EBV Illness In Children: A Double-Blind, Placebo-Controlled Study. International Pediatrics. Vol. 18, No. 3. pp. 164-169.
- ↑ Balfour et al. (May 2007) A virologic pilot study of valacyclovir in infectious mononucleosis. Journal of Clinical Virology. Volume 39, Issue 1. pp. 16-21.
- ↑ Ascherio A, Munger KL. Environmental risk factors for multiple sclerosis. Part I: the role of infection. Ann Neurol. 2007 Apr;61(4):288-99.
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