Associated with Epstein-Barr virus.
EB virus is a gamma herpesvirus with a double stranded DNA genome of about 172 kb.
In approximately 90% of patients with infectious mononucleosis Epstein-Barr virus is the cause.
EB virus infects B lymphocytes leading to activation of a T cell mediated response causing atypical and immature cells in the peripheral blood.
Most cases appear during adolescents and early adulthood.
It is most common in teenagers and young adults in high income countries.
In developing countries EBV infection kids to occur in early childhood and is often asymptomatic or non-specific.
Older adults are less likely to develop infectious mononucleosis because immunity acquired for EBB infection earlier in life.
Over 95% of adults worldwide have serologic evidence of infection with EBV per 100,00 population aged 15-19 years.
Highest incidence in age group 15-24 years.
Rates of infections among those age 15-24 years is about 6-8 cases per 1000 persons per year.
No seasonal or annual cycles in incidence.
No sexual predilection for IM.
30-70% of college freshman are seronegative for EBV, and of these 10-20% each year become infected, and 30-50% of these individuals develop IM. Crawford DH).
Rates of adolescent infection 30 times higher in whites than blacks.
Symptoms are the result of immune response against the virus including cytotoxic T cells, natural killer cells and cytokines, particularly interleukin 10.
Incubation 4-6 weeks and prodromal symptoms of fatigue, malaise and myalgias may occur 1-2 weeks before typical symptomatology.
EBV transmission occurs mainly through exposure to infected saliva-mainly through kissing and less frequently via sexual transmission (Thorley-Lawson DA).
Infection of tonsillar epithelial cells, and B lymphocytes cause viral reproduction and high levels of salivary shedding of EBV.
EBV salivary shedding in IM decreases over the first year of infection but persists for life (Hadinoto V).
Majority of cases occur during primary EBV infection, although chronically infected persons after T-lymphocyte depletion with monoclonal antibodies against CD3 (Keymeulin B).
Latently infected B lympohocytes circulate and are lifelong viral reservoirs expressing a restricted set of EBV genes and mostly inapparent to immune surveillance.
Atypical lymphocytosis of greater than or equal to 10% of cells is a common feature.
CD4 and CD8 T cells are expanded in response to EB virus.
Classic clinical presentation the triad of fever, pharyngitis, and lymphadenopathy.
Splenomeagly, jaundice, and hepatomegaly.
Symptoms may persist for longer than six months and serious complications such as splenic rupture can occur.
Most commonly affects individuals who have had primary EBV infection during or after the second decade of life.
Fever generally occurs during the first two weeks and can last up to 1 months.
Lymphadenopathy most often affects the posterior cervical nodes, but can be at any site.
Almost all patients with mononucleosis have anterior cervical adenopathy, but the posterior cervical adenopathy is more specific for the disease, as are axillary and inguinal adenopathy.
Pharyngitis most common during the first 2 weeks of the illness.
Sore throat and malaise most common presenting symptoms.
Lymphoid hyperplasia and mucosal edema may lead to upper airway obstruction in 1% of cases.
Periorbital edema, palate petechiae and rash may occur.
Can present with the morbilliform or maculopapular rash in up to 13% of cases.
The incidence of rash increases with the coadministration of antibiotics, particularly ampicillin and amoxicillin.
About 30% of patients who have received at least one dose of amoxicillin manifest a hypersensitivity rash.
Splenomegaly seen in 52% of patients and occurs during the second and third weeks of the illness.
Splenomegaly is seen almost in all cases on ultrasonography.
Some patients may develop vaginal ulcers (Leigh R).
Splenic rupture can occur in 0.5-1% of cases.
About 25-50% of patients have hematologic abnormalities and include: hemolytic anemia, thrombocytopenia, aplastic anemia, disseminated intravascular coagulation, and thrombotic thrombocytopenic purpura.
Neurologic complications occur in 1-5% of cases and include: aseptic meningitis, facial nerve palsy, Guillain-Barre syndrome, transverse myelitis, peripheral neuritis, meningoencephalitis, cerebeller inflamation and optic neuritis.
Majority of patients have no apparent sequelae following the infection.
Most patients have resolution of clinical and laboratory abnormalities by one month, although neck lymphadenopathy and associated fatigue may persist.
Fatigue may persist for 6 months, but most patients can resume normal activities by 2-3 months.
When associated with cold agglutinin disease the antibody is to the i antigen.
EBV infection may rarely trigger the hematophagocytic lymphohistiocytosis syndrome with hepatosplenomegaly, lymphadenopathy, prolonged fever, rash, pancytopenia, and liver function impairment.
A rare X-linked male lymphoproliferative syndrome associated with a normal phenotype until exposed to EBV can result in a severe or fatal mononucleosis.
The gene associated with the above X-linked is the SH2D1A and mutation of the gene causes increase T cell CD8+ proliferation.
Survivors of the above may be associated with a B cell lymphoma and hypogammaglobulinemia.
No antiviral medications are effective.
Benefit in controlled trials with the use of corticosteroids has not been proven, but their use may be helpful with tonsillar enlargement and acute airway obstruction.
Differential diagnosis includes: cytomegalic virus, toxoplasmosis, adenovirus infection, HIV infection, and acute leukemia.
Early in the disease antibody tests for mononucleosis is more likely to produce false negative results.
False negative results are more common in younger children.