Epstein-Barr Virus (EBV)

EBV is the cause of infectious mononucleosis (also termed "mono"), an illness associated with symptoms and signs like fever, fatigue, swollen tonsils, headache, and others

• The virus was first discovered in 1964 when Sir Michael Anthony Epstein and Ms. Yvonne Barr found it in a Burkitt lymphoma cell line. In 1968, the virus was linked to the disease of infectious mononucleosis (glandular fever).
• Infection with Epstein-Barr virus (EBV) is common and usually occurs in childhood or early adulthood.
• EBV is the cause of infectious mononucleosis (also termed "mono"), an illness associated with symptoms and signs like:
  • fever,
  • fatigue,
  • swollen tonsils,
  • headache, and
  • sweats,
  • sore throat,
  • swollen lymph nodes in the neck, and
  • sometimes an enlarged spleen (BPH, benign prostatic hyper dysplasia),
• It is also known as human herpesvirus⁴. Although EBV can cause mononucleosis, not everyone infected with the virus will get mononucleosis. White blood cells called B cells are the primary targets of EBV infection.
• Less commonly, EBV can cause more serious diseases. Symptoms caused by EBV are usually mild and self-limited, but the virus persists in the body for life. It can be reactivated quietly without causing symptoms and may contaminate saliva. Thus, otherwise healthy people can spread the virus to uninfected people through kissing or sharing food. This is why mononucleosis is referred to as the "kissing disease." EBV probably plays a role in the development of some cancers, including certain lymphomas and nasopharyngeal cancer.
• No specific treatments cure mononucleosis caused by EBV.

Once the Epstein-Barr virus is acquired (spread from person to person), it takes about four to six weeks for symptoms to appear. Children usually have nonspecific symptoms or no symptoms at all. Rarely, young children may have rashes, pneumonia, or low white blood counts.

Many teenagers and young adults develop symptoms of mononucleosis. Acute mononucleosis causes:

• sore throat,
• fever,
• fatigue, and
• swollen lymph nodes.

A sore throat caused by the virus is very painful and is the usual reason for infected people to seek medical attention. Signs and symptoms of mono include:

• swollen tonsils,
• loss of appetite,
• fatigue,
• chills,
• headache,
• bloating,
• sore muscles,
• body aches,
• weakness, and
• sweats.
• Some people may have dizziness.

Although the symptoms fade in days to weeks, some people complain of fatigue that lasts for weeks after infection, though most people eventually recover completely.

Rash

A small percentage of people develop a rash due to the infection. A rash can also develop in people with mononucleosis who are given ampicillin or amoxicillin. This common reaction does not necessarily mean the patient is allergic to penicillin or related antibiotics.

The appearance of the rash in conjunction with the above symptoms and signs also can lead to misdiagnosis of EBV.

Enlarged Spleen

The spleen becomes swollen in up to half of the people with mononucleosis. The spleen is always engorged with blood, and if it ruptures, it can cause a person with the virus to bleed to death. Blunt trauma to the abdomen, even mild trauma, may result in a splenic rupture if swollen. People with mono are usually advised not to play sports, especially any contact sports. The spleen may also rupture spontaneously.

Neurological Complications

A very small number of infected people have neurological complications. These include inflammation of the brain (encephalitis), of the lining of the brain (meningitis), or of individual nerves. Less commonly, infection of the spinal cord may occur. The majority of patients with neurological complications recover completely. Rarely, other organs may be involved, including the lungs or heart.

X-linked Lymphoproliferative Syndrome in Boys

Rarely, boys may develop an overwhelming infection with EBV known as X-linked lymphoproliferative syndrome. In X-linked lymphoproliferative syndrome, the number of immune cells or lymphocytes (B cells) in the body increases substantially. The lymphocytes infiltrate major organs, often causing severe liver disease or death. Lymphoproliferative syndrome is probably a result of a subtle genetic defect that makes it difficult for the immune system to contain the virus. Organ transplants or bone marrow transplants are also risk factors for developing lymphoproliferative syndrome.

Cancer

In addition to lymphoproliferative syndrome, EBV is considered a risk factor for some cancers. One such cancer is lymphoma of the brain. Lymphoma of the brain is most common in people with advanced AIDS but also occurs in other immunosuppressed states. Nasopharyngeal cancer, Burkitt lymphoma (a type of non-Hodgkin lymphoma), and some types of Hodgkin's lymphoma are also associated with EBV. The exact mechanism by which EBV helps to transform normal lymphocytes into cancer cells is not fully understood.

Leukoplakia

EBV is associated with a condition called oral hairy leukoplakia. This is a white plaque on the side of the tongue that cannot be removed by gentle scraping. It is most common in people with AIDS or other immunosuppressive states.

Misdiagnosis

Mononucleosis causes fatigue, which can sometimes last for weeks or even longer. Therefore, chronic infection with EBV (CEBV) has been investigated as a cause of chronic fatigue syndrome (CFS), also called systemic exertion intolerance disease (SEID). Studies to date have not been able to find a causal link between EBV and CFS. In CFS, there is a chronic lack of energy often associated with difficulty concentrating or generalized pain.

Chronic Fatigue Syndrome (CFS)

CFS is more common among women than men and occurs in early to middle adulthood. Blood tests are usually normal. There is no specific diagnostic test for CFS, and the cause remains unknown.

During Pregnancy

During pregnancy, it is rare for a fetus to become infected with EBV even if the mother is infected. Even among women who do become infected while pregnant, there are no documented birth defects that have resulted.

Associated Diseases

EBV is also associated with several autoimmune diseases, including multiple sclerosis, autoimmune thyroiditis, systemic lupus erythematosus, oral lichen planus (OLP), rheumatoid arthritis (RA), autoimmune hepatitis, Sjögren's syndrome, and Kawasaki disease.

EBV is a contagious virus that is transmitted from person to person and occurs throughout the world. The cause of infection is generally close person-to-person contact through bodily fluids, especially saliva. It may also be transmitted during sexual contact through semen, and can also be spread by blood transfusions or organ transplants.

The virus contains double-stranded DNA and multiplies in white blood cells (a certain type of lymphocyte called a B cell) and other cells, such as those lining the mouth, tongue, and nose. The human immune system usually contains the virus effectively, reducing but not eliminating the virus. A few living viruses will persist in a line of lymphocytes for the rest of the person's life. This is known as a "latent" infection (inactive stage). Occasionally, the virus may multiply (reactivate), but this does not cause symptoms unless the person's immune response system is not working properly.

Most people in the U.S. have been infected with EBV, mononucleosis is more common in whites than in the African-American populations.

Some risk factors associated with acquiring EBV include being female, living in tropical countries, having immunodeficiency, and being sexually active.

Mild symptoms of EBV infection may be treated at home. See a doctor if you experience:

• a prolonged fever,
• abdominal pain,
• a severe headache,
• difficulty breathing, and/or
• jaundice (a yellowish discoloration of the skin or eyes).

The diagnosis of mononucleosis starts with a detailed history and physical examination. The doctor will look for fever, an inflamed or sore throat, swollen lymph nodes in the neck, and an enlarged spleen. Red dots (petechiae) may be seen on the palate. Up to half of the infected people will have an enlarged spleen, and 10% will have an enlarged liver on abdominal examination.

People with suspected mononucleosis will have a blood sample drawn for blood counts and a "mono spot" test. If the mono spot is positive, the diagnosis is confirmed. Mono spots may be falsely negative in children under 4 years of age or in the elderly. Repeating the test at a later date may be helpful in these cases. Other viruses and pathogens may cause an illness that is similar to mononucleosis (for example, cytomegalovirus, adenovirus, and Toxoplasma), so additional blood may be drawn to test for other pathogens.

In infected people, the number of normal lymphocytes (B cells) in the blood is usually increased and the cells may look unusual or "atypical" under the microscope. Approximately 1%-3% of people develop anemia, which is caused by the destruction of the red blood cells (hemolysis). Platelet counts may be low in up to half of patients, although this does not usually result in bleeding. In some cases, blood cells may be destroyed by other blood cells (hemophagocytic syndrome). Mild elevations in liver enzymes in the blood are common.

Several antibody tests are available to determine if a person has had a past infection or a current/recent infection with EBV. Some antibodies occur early and are transient, thus indicating a new or "acute" infection. These include IgM antibodies to the viral capsid antigen (VCA). Some antibodies develop immediately and persist for life, such as the IgG antibody to the viral capsid antigen. Other antibodies develop three to four weeks into the illness and persist for life, including antibodies to the nuclear antigen (EBNA). Antibodies to early antigen (EA-IgG) may arise during acute infection and may persist, go away, or recur. PCR tests that detect EBV DNA are available in some laboratories.

Many physicians use three laboratory criteria (lymphocytosis, 10% or more lymphocytes are atypical on a peripheral blood smear and a positive serologic test for EBV) along with the history and physical findings listed above to confirm a diagnosis of acute infectious mononucleosis. About 90% of adults have antibodies indicating that they had infections in the past.

There is no specific medicine to treat mononucleosis. Some physicians use corticosteroids to treat significant swelling in the throat or an enlarged spleen, but steroids are not needed in most people. Antiviral medications are available to help oral hairy leukoplakia, including acyclovir (Zovirax), ganciclovir (Cytovene), and foscarnet (Foscavir).

People with acute mononucleosis usually recover completely and do not need prolonged follow-up. The exceptions are people with an enlarged spleen who should be followed until this resolves. The few individuals who develop chronic neurological changes usually have follow-up with a neurologist.

Rest, fluids, and over-the-counter pain and fever-reducer medicines are recommended for people with mononucleosis. Follow the directions that come with the medications. Many over-the-counter medications for adults are not recommended for children.

Avoid potential trauma to the spleen, including contact sports, for at least one month or until the spleen is no longer enlarged, whichever is longer.

The prognosis for Epstein-Barr virus infection is good. Almost all people infected with EBV recover completely in about 1-3 months. Neurological changes usually completely resolve, although a few adults may have some deficits.

Although most infections become latent, most remain asymptomatic. There are ongoing efforts to develop a vaccine against EBV—both vaccines to prevent primary infection or disease, or therapeutic vaccines to treat EBV malignancies—but these have not been successful to date. New medications are being developed to treat mononucleosis and EBV.

People with acute mononucleosis usually recover completely and do not need prolonged follow-up. The exceptions are people with an enlarged spleen who should be followed until this resolves. The few individuals who develop chronic neurological changes usually have follow-up with a neurologist.

Most people will acquire EBV at some point in their lives; it is very difficult to prevent infection. It has been recommended that people with mononucleosis refrain from donating blood until at least six months after recovery. People who have had hepatitis caused by EBV will usually not be permitted to donate blood.

For Epstein-Barr virus, you may be treated by a primary care provider (PCP), such as a family practitioner, an internist, or a child's pediatrician.

If the symptoms of EBV become chronic, you may be referred to an infectious-disease specialist or an immunologist (also called an allergist/immunologist).

You may need to see a neurologist for EBV-related neurological complications. If the spleen becomes enlarged, you may be referred to a hematologist, and if EBV leads to cancer, you may see an oncologist.

"Epstein-Barr Virus and Infectious Mononucleosis," CDC
http://www.cdc.gov/epstein-barr/index.html

"Pediatric Mononucleosis and Epstein-Barr Virus Infection," Medscape.com
http://emedicine.medscape.com/article/963894-overview