Infectious mononucleosis

Infectious mononucleosis
Specialty	Infectious diseases

Infectious mononucleosis, also known as Pfeiffer's disease, mono (in North America) and more commonly known as glandular fever in other English-speaking countries. It occurs most commonly in adolescents and young adults, where it is characterized by fever, sore throat, muscle soreness, and fatigue. Infectious mononucleosis typically produces a mild illness in small children, and is often asymptomatic. Mononucleosis is predominantly caused by the Epstein-Barr virus (EBV), which infects B cells (B-lymphocytes), producing a reactive lymphocytosis predominantly consisting of atypical lymphocytes, a specific type of T-cell that gives the disease its name.

The misnomer "kissing disease" is often applied to mono, as in developed countries it is most common at the same age when adolescents and young adults are initiating romantic behavior. This co-occurence is not apparent in undeveloped countries, where poor sanitation and close living arrangements cause the causative virus to be spread at a much earlier age, when the disease is mild and seldom diagnosed.

Symptoms

• 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.
• Sore throat—White patches on the tonsils and back of the throat are often seen
• Muscle weakness and Mental fatigue (sometimes extreme)

Additional Symptoms Include:

• 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.
• Aching muscles
• Headache
• Loss of appetite
• Depression
• Diarrhea
• Dizziness or disorientation
• Uncontrolled shaking at times
• Unable to swallow due to enlarged tonsils
• 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 hence the longer s/he 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 most cases of mononucleosis are caused by the E.B. virus, the condition is defined by the clinical presentation and laboratory findings. Cytomegalovirus can produce a similar illness, usually with less throat pain, and also generate atypical lymphocyte proliferation. In recent years, as precise virological and serological studies are more commonly done to identify the actual causative virus, some clinicians have taken to use "mononucleosis" to refer only to the E.B. virus cases. Symptoms similar to those of mononucleosis can also be caused by adenovirus, acute HIV infection and the protozoan Toxoplasma gondii.

Diagnosis

Peripheral blood smear (low power) showing lymphocytosis from a 16-year-old male with pharyngitis and positive monospot test.

Laboratory findings usually include an elevated white blood cell count and abnormal liver function tests. The white cell count elevation is predominantly in the lymphocyte portion, and of those the majority is often of the atypical form characteristic of the disease.

Specific tests for EBV include:

• A monospot test (positive for infectious mononucleosis)
• Epstein-Barr virus antigen by immunofluorescence (positive for EBV)
• Epstein-Barr virus antibody titers to help distinguish acute infection from past infection with EBV

Transmission

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. Individuals in close living arrangements rarely pass the infection on to each other, although symptoms may not present for months or even years. Generally Mono is not spread within households because the only way to spread mono is through direct saliva contact. As with many viral infections, such as chicken pox, antibodies are developed by individuals who become infected with the disease and recover. In most individuals, these antibodies remain in their system, creating lifelong immunity to further infections.

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 (CFS), although CFS is a distinct condition from IM. Still, current studies suggest there is an association between infectious mononucleosis and 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. "Chronic fatigue states" as defined by the CDC criteria for CFS, appear to occur in 10% of those who contract mononucleosis. Chronic fatigue may then be a rather common side effect of infectious mononucleosis. On the other hand, studies conducted by the CDC and others have discounted a link between EBV and CFS.

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. 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. 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. Microglia may remain activated or "damaged" for months following infection, thereby causing a slowly dissipating fatigue. Secondary infections can occur. Such infections include mild swelling of the cartilage between the sternum and ribs occurring approximately one month after initial diagnosis.

Treatment

Infectious mononucleosis is generally self-limiting and only symptomatic and/or supportive treatments are used. 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.

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 but may be useful if there is a risk of airway obstruction, severe thrombocytopenia, or hemolytic anemia.

There is little evidence to support the use of aciclovir, although it may reduce initial viral shedding. 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. 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.

Morbidity and mortality

Fatalities from mononucleosis are near impossible in developed nations. 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), but this has not been affirmed.
• Hematologic: EBV can cause autoimmune hemolytic anemia (direct Coombs test is positive) and various cytopenias.