September 17, 2011

The term mononucleosis refers to both a specific infection and a syndrome, with considerable overlap between the two. Acute Epstein-Barr virus (EBV) infection produces an illness characterized by sore throat, swollen lymph glands, fatigue, and fever. The clinical illness produced by acute EBV infection is called mononucleosis; the term is also used when other infectious agents produce a similar illness. Epstein-Barr virus is a member of the herpesvirus family, which also includes herpes simplex I and II, cytomegalovirus (CMV), discussed below, and varicella-zoster virus, the cause of chicken pox and shingles. Infection due to this family of viruses is characterized by an acute illness followed by lifelong infection, which is usually clinically silent (although chronic infection, and relapses due to immunosuppression can occur).

Infection with Epstein-Barr virus usually occurs during adolescence or early adulthood. The virus is found in saliva, and is spread by kissing, shared beverages, or other close contact. Fever, sore throat, and swollen lymph nodes, particularly in the neck area, are the most typical signs and symptoms. Enlargement of the spleen (splenomegaly) is also common. The clinical presentation can be quite varied and is somewhat dependent on age. Signs and symptoms of acute Epstein-Barr virus infection occurring in older individuals (in this case, over 30) are often atypical, and individuals may not have the classic symptoms of sore throat and adenopathy. In children younger than 5, acute Epstein-Barr virus infection often produces a mild, nonspecific illness. Epstein-Barr virus infects lymphocytes and infection results in the presence of significant numbers of abnormal-appearing white blood cells (referred to as atypical lymphocytes). The absence of atypical lymphocytes makes acute Epstein-Barr virus infection highly unlikely, and the presence of significant numbers of atypical lymphocytes strongly suggests the diagnosis. Individuals often have mild elevations in liver function tests (LFTs), but LFTs that are increased by more than five times the normal level are unusual, and should prompt investigation for alternative diagnoses.

Individuals can be quite symptomatic from acute Epstein-Barr virus infection, and the symptoms often last 2-3 weeks. Swelling in the lymph nodes and tonsils can be significant, and in rare cases may produce obstruction of the upper airway. The most common complication of acute Epstein-Barr virus infection is significant fatigue following the acute illness; it is not unusual for individuals to have fatigue for several months following the initial symptoms. Another complication is splenic rupture; spontaneous splenic rupture is rare but individuals with splenomegaly should refrain from activity that produces trauma to the abdomen such as contact sports. Other complications are rare and include encephalitis (brain swelling), hemolytic anemia (low red blood cells), and myocarditis (swelling of the heart muscle).

Therapy of acute Epstein-Barr virus infection is largely supportive and there is no role for antivirals in routine cases. Corticosteroids have been used when marked lymphadenopathy (lymph node swelling) and tonsil swelling threaten the upper airway. The role of Epstein-Barr virus in chronic fatigue syndrome (CFS) remains unproven, and most evidence suggests that there is no direct relationship between Epstein-Barr virus and chronic fatigue syndrome. Patients with chronic fatigue syndrome often have elevated levels of antibodies to Epstein-Barr virus, but similar levels occur in many asymptomatic individuals. The existence of “chronic Epstein-Barr,” defined by symptoms of fatigue that last more than a year following acute infection, or persistent fatigue without acute infection, remains doubtful. In highly immunosuppressed patients Epstein-Barr virus infection is associated with the development of lymphoma, particularly in patients with organ transplants and advanced HIV infection.

About 5% of cases of the mononucleosis syndrome (fever, sore throat, adenopathy, and atypical lymphocytes) are due to causes other than Epstein-Barr virus. The most common alternative agent is cytomegalovirus, which can produce a similar illness, although marked adenopathy (lymph node swelling) is unusual and the percentage of atypical lymphocytes (white blood cells) is much smaller (20%). Acute infection with cytomegalovirus can be minimally symptomatic, and can also produce an illness characterized by persistent low-grade fever and fatigue. cytomegalovirus can produce significant illness in immunosuppressed patients, and is a major cause of morbidity and mortality in AIDS patients and organ transplant patients. Acute infection with the parasite Toxoplasma gondii can also produce mononucleosis-like illness.

SEE ALSO: Shingles

Suggested Reading

  • Cohen, J. I. (2000). Medical progress: Epstein-Barr virus infection. New England Journal of Medicine, 343, 481-492.
  • Schooley, R. T. (2000). Epstein-Barr virus (infectious mononucleosis). In G. L. Mandell, J. E. Bennett, & R. Dolin (Eds.), Principles and practices of infectious diseases (5th ed., pp. 1599-1608). New York: Churchill Livingstone.


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