Infectious Mononucleosis: Pathogenesis, Symptoms and Treatment

Infectious mononucleosis is a self-limiting lymphoproliferative disorder caused by the Epstein-Barr virus (Human Herpes type 4), a member of the herpesvirus family. This condition is characterized by fatigue, fever, pharyngitis, and lymphadenopathy.

Infectious mononucleosis may occur at any age but occurs principally in adolescents and young adults in developed countries. EBV is one of the most successful viruses in evading the immune system, infecting about 90% of humans and persisting for the lifetime of the person.

EBV spreads from person to person primarily through contact with infected oral secretions.

Transmission requires close contact with infected persons. Thus, the virus spreads readily among young children in crowded conditions, where there is considerable sharing of oral secretions. Kissing is also an effective mode of transmission, hence the term “kissing disease."

Pathogenesis of infectious mononucleosis

Infectious mononucleosis is largely transmitted through oral contact with EBV-contaminated saliva.

The virus initially penetrates the nasopharyngeal, oropharyngeal, and salivary epithelial cells. It then spreads to the underlying oropharyngeal lymphoid tissue and, more specifically, to B lymphocytes, all of which have receptors for EBV.

Infection of the B cells may take one of two forms; it may kill the infected B cell, or the virus may incorporate itself into the cell’s genome.

The B cells that harbor the EBV genome proliferate in the circulation and produce the well-known heterophil antibodies that are used for the diagnosis of infectious mononucleosis. A heterophil antibody is an immunoglobulin that reacts with antigens from another species, in this case, sheep red blood cells.

The normal immune response is important in controlling the proliferation of the EBV-infected B cells and cell-free virus. Most important in controlling the proliferation of EBV-infected B cells are the CD8, cytotoxic T cells and NK cells. These virus-specific T cells appear as large, atypical lymphocytes that are characteristic of the infection.

In otherwise healthy persons, the humoral and cellular immune responses serve to control viral shedding by limiting the number of infected B cells rather than eliminating them.

Although infected B cells and free virions disappear from the blood after recovery from the disease, the virus remains in a few transformed B cells in the oropharyngeal region and is shed in the saliva. Once infected with the virus, persons remain asymptomatically infected for life, and a few such persons intermittently shed EBV.

Immunosuppressed persons shed the virus more frequently. Asymptomatic shedding of EBV by healthy persons is thought to account for most of the spread of infectious mononucleosis, despite the fact that it is not a highly contagious disease

Clinical Signs and Symptoms

In most young children, primary EBV infection is asymptomatic.

The onset of infectious mononucleosis usually is insidious with an incubation period of 4 to 8 weeks.

The triad of fever, pharyngitis, and lymphadenopathy is usually present. Occasionally, the disorder comes on abruptly with a high fever which usually peaks in the afternoon or early evening.

Pharyngitis may be severe, painful, and exudative and may resemble streptococcal pharyngitis.

Adenopathy is usually symmetric and may involve any group of nodes, particularly the anterior and posterior cervical chains. Adenopathy may be the only manifestation

Hepatitis and splenomegaly are common manifestations of the disease and are thought to be immune-mediated.
Hepatitis is characterized by mild hepatic percussion tenderness, nausea, anorexia, and jaundice. Although discomforting, it usually is a benign condition that resolves without causing permanent liver damage.

Splenomegaly and rupture of the spleen is an infrequent complication.

The peripheral blood usually shows an increase in the number of leukocytes, with a white blood cell count between 12,000 and 18,000 cells/L, 60% of which are lymphocytes.12 The rise in white blood cells begins during the first week, continues during the second week of the infection, and then returns to normal around the fourth week.

Atypical lymphocytes are common, constituting more than 20% of the total lymphocyte count. Heterophil antibodies usually appear during the second or third week and decline after the acute illness has subsided. They may, however, be detectable for up to 9 months after the onset of the disease.

Some degree of debility and lethargy may persist for 2 to 3 months.

Diagnosis

Clinical history and physical examination.

Laboratory diagnosis involves a complete blood count and EBV serologic testing. Lymphocytes that are morphologically atypical are present.

HIV RNA viral blood count, p24 antigen assay, and CD4 count should be done in patients at risk.

Heterophil antibodies are measured using card-agglutination (monospot) tests.

Treatment of infectious mononucleosis

Most persons with infectious mononucleosis recover without incident. The acute phase of the illness usually lasts for 2 to 3 weeks, after which recovery occurs rapidly.

Treatment is primarily symptomatic and supportive.

It includes bed rest and analgesics such as aspirin to relieve the fever, headache, and sore throat.

Corticosteroids can be helpful for complications such as impending airway obstruction, severe thrombocytopenia, and hemolytic anemia.

Complications:

Neurologic complications are rare but may include encephalitis, seizures, Guillain-Barre syndrome, peripheral neuropathy, aseptic meningitis, myelitis, cranial nerve palsies, and psychosis.

Hematologic complications are usually self-limited. They include granulocytopenia, thrombocytopenia, and hemolytic anemia. Hemolytic anemia is often due to anti-i-specific antibodies.

Splenic rupture can result from splenic enlargement and capsular swelling, which are maximal 10 to 21 days after presentation.

Respiratory complications include, rarely, upper airway obstruction due to pharyngeal or paratracheal lymphadenopathy; respiratory complications may respond to corticosteroids.

Clinically silent interstitial pulmonary infiltrates occur mostly in children and are usually visible on x-rays.

Hepatic complications include elevated aminotransferase levels. If jaundice or more severe enzyme elevations occur, other causes of hepatitis should be investigated.

Overwhelming infection with EBV occurs sporadically but may cluster in families, particularly those with X-linked lymphoproliferative syndrome. Survivors of overwhelming primary EBV infection are at risk of developing agammaglobulinemia or lymphoma.