Infectious mononucleosis

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. Around 90% of people will acquire the virus even if they exhibit no symptoms. Most of the time subjects show symptoms. Infectious Mononucleosis typically produces a very mild illness in small children, but is typically asymptomatic. 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, earning it the name "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. Mono is not spread through the air. It is even possible to live in the same house with a person and never acquire the virus. In rare cases a person may have a high resistance to infection.^{[citation needed]} 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 infectious mononucleosis, this can rise to 50-70%. Also, the total white blood count may increase to 10,000-20,000 per cubic millimeter.

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Symptoms

  Symptoms usually appear 4-6 weeks after exposure to infected other, 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 - a possible symptom of a potentially fatal rupture of the spleen.^[1]
• Aching muscles
• Headache
• Loss of appetite
• Depression
• Weakness
• Skin rash
• Dizziness or disorientation
• Uncontrolled shaking at times
• Dry cough
• 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. This is especially true in children, in whom infection seldom causes more than a very mild cold which often goes undiagnosed. Children are typically just carriers of the disease. 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.

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.^{[citation needed]} 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. Some adult 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)^{[citation needed]}. 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.^[2] "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 are triggered by the acute infection.^{[citation needed]} 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.

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 as they are ineffective against viral infections. The antibiotics amoxicillin and ampicillin are contraindicated in the case of any coinciding bacterial infections during mononucleosis because 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 (with the exception of the two mentioned above) should be administered to treat the strep throat. 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 proposed 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.

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