There are several forms of

Epstein–Barr virus The Epstein–Barr virus (EBV), formally called ''Human gammaherpesvirus 4'', is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus. It is b ...

(EBV) infection. These include asymptomatic infections, the primary infection,

infectious mononucleosis Infectious mononucleosis (IM, mono), also known as glandular fever, is an infection usually caused by the Epstein–Barr virus (EBV). Most people are infected by the virus as children, when the disease produces few or no symptoms. In young adult ...

, and the progression of asymptomatic or primary infections to: 1) any one of various Epstein–Barr virus-associated lymphoproliferative diseases such as

chronic active EBV infection Chronic active EBV infection or in its expanded form, chronic active Epstein–Barr virus infection is a very rare and often fatal complication of Epstein–Barr virus (EBV) infection that most often occurs in children or adolescents of Asian or S ...

, EBV+

hemophagocytic lymphohistiocytosis Hemophagocytic lymphohistiocytosis (HLH), also known as haemophagocytic lymphohistiocytosis (British spelling), and hemophagocytic or haemophagocytic syndrome, is an uncommon hematologic disorder seen more often in children than in adults. It is a ...

Burkitt's lymphoma Burkitt lymphoma is a cancer of the lymphatic system, particularly B lymphocytes found in the germinal center. It is named after Denis Parsons Burkitt, the Irish surgeon who first described the disease in 1958 while working in equatorial Africa. ...

, and

Epstein–Barr virus positive diffuse large B-cell lymphoma, not otherwise specified Epstein–Barr virus positive diffuse large B-cell lymphoma, not otherwise specified (also termed: EBV positive diffuse large B cell lymphoma, NOS; EBV+ DLBCL, NOS; or EBV+ DLBCL) was initially termed in the WHO 2008 classification as Epstein–Ba ...

); 2) non-lymphoid cancers such as Epstein–Barr virus associated gastric cancer, soft tissue

sarcoma A sarcoma is a malignant tumor, a type of cancer that arises from transformed cells of mesenchymal (connective tissue) origin. Connective tissue is a broad term that includes bone, cartilage, fat, vascular, or hematopoietic tissues, and sarcom ...

leiomyosarcoma Leiomyosarcoma is a malignant (cancerous) smooth muscle tumor. A benign tumor originating from the same tissue is termed leiomyoma. While leiomyosarcomas are not thought to arise from leiomyomas, some leiomyoma variants' classification is evolvi ...

, and

nasopharyngeal cancer Nasopharyngeal carcinoma (NPC), or nasopharynx cancer, is the most common cancer originating in the nasopharynx, most commonly in the postero-lateral nasopharynx or pharyngeal recess ( fossa of Rosenmüller), accounting for 50% of cases. NPC occurs ...

s; and 3) Epstein–Barr virus-associated non-lymphoproliferative diseases such as some cases of the

immune disorder An immune disorder is a dysfunction of the immune system. These disorders can be characterized in several different ways: * By the component(s) of the immune system affected * By whether the immune system is overactive or underactive * By whether t ...

s of

multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...

and

systemic lupus erythematosis Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Comm ...

and the childhood disorders of

Alice in Wonderland Syndrome Alice in Wonderland syndrome (AIWS), also known as Todd's syndrome or dysmetropsia, is a neuropsychological condition that causes a distortion of perception. People may experience distortions in visual perception of objects, such as appearing sma ...

and acute cerebellar ataxia.

Symptoms

Symptoms of

are

fever Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...

sore throat Sore throat, also known as throat pain, is pain or irritation of the throat. Usually, causes of sore throat include * viral infections * group A streptococcal infection (GAS) bacterial infection * pharyngitis (inflammation of the throat) * tonsi ...

, and swollen

lymph glands A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that include ...

. Sometimes, a swollen

spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .

liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...

involvement may develop.

Heart The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide t ...

problems or involvement of the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

occurs only rarely, and infectious mononucleosis is almost never fatal. There are no known associations between active EBV infection and problems during pregnancy, such as miscarriages or birth defects. Although the symptoms of infectious mononucleosis usually resolve in 1 or 2 months, EBV remains dormant or latent in a few cells in the throat and blood for the rest of the person's life. Periodically, the virus can reactivate and is commonly found in the saliva of infected persons. Reactivated and post-latent virus may pass the

placental barrier The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate materna ...

in (also

seropositive Serostatus refers to the presence or absence of a serological marker in the blood. The presence of detectable levels of a specific marker within the serum is considered seropositivity, while the absence of such levels is considered seronegativity. ...

) pregnant women via

macrophages Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...

and therefore can infect the fetus. Also re-infection of prior seropositive individuals may occur. In contrast, reactivation in adults usually occurs without symptoms of illness. EBV also establishes a lifelong dormant infection in some cells of the body's immune system. A late event in a very few carriers of this virus is the emergence of Burkitt's lymphoma and nasopharyngeal carcinoma, two rare

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

s. EBV appears to play an important role in these

malignancies Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...

, but is probably not the sole cause of disease. Most individuals exposed to people with infectious mononucleosis have previously been infected with EBV and are not at risk for infectious mononucleosis. In addition, transmission of EBV requires intimate contact with the saliva (found in the mouth) of an infected person. Transmission of this virus through the air or blood does not normally occur. The incubation period, or the time from infection to appearance of symptoms, ranges from 2 to 6 weeks with 4 weeks being the most common. Persons with infectious mononucleosis may be able to spread the infection to others for a period of weeks. However, no special precautions or isolation procedures are recommended, since the virus is also found frequently in the saliva of healthy people. In fact, many healthy people can carry and spread the virus intermittently for life. These people are usually the primary reservoir for person-to-person transmission. For this reason, transmission of the virus is almost impossible to prevent. The clinical diagnosis of infectious mononucleosis is suggested on the basis of the symptoms of fever, sore throat, swollen lymph glands, and the age of the patient. Usually, laboratory tests are needed for confirmation. Blood test results for persons with infectious mononucleosis include an elevated

white blood cell White blood cells, also called leukocytes or leucocytes, are the cell (biology), cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and de ...

count, an increased percentage of atypical mononuclear cells. Liver enzymes are often elevated. A positive "mono spot" test is useful in confirming the diagnosis but a negative result does not rule out primary EBV infection.

EBV-associated diseases

Chronic active EBV infection Chronic active EBV infection or in its expanded form, chronic active Epstein–Barr virus infection is a very rare and often fatal complication of Epstein–Barr virus (EBV) infection that most often occurs in children or adolescents of Asian or S ...

* Epstein–Barr virus-associated lymphoproliferative diseases *

Hodgkin's disease Hodgkin lymphoma (HL) is a type of lymphoma, in which cancer originates from a specific type of white blood cell called lymphocytes, where multinucleated Reed–Sternberg cells (RS cells) are present in the patient's lymph nodes. The condition wa ...

Acute kidney injury Acute kidney injury (AKI), previously called acute renal failure (ARF), is a sudden decrease in kidney function that develops within 7 days, as shown by an increase in serum creatinine or a decrease in urine output, or both. Causes of AKI are cla ...

Alice in Wonderland syndrome Alice in Wonderland syndrome (AIWS), also known as Todd's syndrome or dysmetropsia, is a neuropsychological condition that causes a distortion of perception. People may experience distortions in visual perception of objects, such as appearing sma ...

Common variable immunodeficiency Common variable immunodeficiency (CVID) is an immune disorder characterized by recurrent infections and low antibody levels, specifically in immunoglobulin (Ig) types IgG, IgM and IgA. Symptoms generally include high susceptibility to foreign i ...

(CVID) *

Hairy leukoplakia Hairy leukoplakia is a white patch on the side of the tongue with a corrugated or hairy appearance. It is caused by Epstein-Barr virus (EBV) and occurs usually in persons who are immunocompromised, especially those with human immunodeficiency v ...

Hepatitis Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pa ...

Herpangina Herpangina, also called mouth blisters, is a painful mouth infection caused by coxsackieviruses. Usually, herpangina is produced by one particular strain of coxsackie virus A (and the term "herpangina virus" refers to coxsackievirus A), but it can ...

Infectious mononucleosis Infectious mononucleosis (IM, mono), also known as glandular fever, is an infection usually caused by the Epstein–Barr virus (EBV). Most people are infected by the virus as children, when the disease produces few or no symptoms. In young adult ...

Kikuchi's disease Kikuchi disease was described in 1972 in Japan. It is also known as histiocytic necrotizing lymphadenitis, Kikuchi necrotizing lymphadenitis, phagocytic necrotizing lymphadenitis, subacute necrotizing lymphadenitis, and necrotizing lymphadenitis. K ...

Multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...

(higher risk in patients infected as teenagers than as children) *

Nasopharyngeal cancer Nasopharyngeal carcinoma (NPC), or nasopharynx cancer, is the most common cancer originating in the nasopharynx, most commonly in the postero-lateral nasopharynx or pharyngeal recess ( fossa of Rosenmüller), accounting for 50% of cases. NPC occurs ...

* Several

Non-Hodgkin's lymphoma Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, is a group of blood cancers that includes all types of lymphomas except Hodgkin lymphomas. Symptoms include lymphadenopathy, enlarged lymph nodes, fever, night sweats, weight los ...

s, including

and primary cerebral lymphoma *

Post-transplant lymphoproliferative disorder Post-transplant lymphoproliferative disorder (PTLD) is the name given to a B cell proliferation due to therapeutic immunosuppression after organ transplantation. These patients may develop infectious mononucleosis-like lesions or polyclonal polymor ...

* Smooth muscle tumors *

Stevens–Johnson syndrome Stevens–Johnson syndrome (SJS) is a type of severe skin reaction. Together with toxic epidermal necrolysis (TEN) and Stevens–Johnson/toxic epidermal necrolysis (SJS/TEN), it forms a spectrum of disease, with SJS being less severe. Erythema ...

* Subepithelial Infiltrates *

New daily persistent headache New daily persistent headache (NDPH) is a primary headache syndrome which can mimic chronic migraine and chronic tension-type headache. The headache is daily and unremitting from very soon after onset (within 3 days at most), usually in a person ...

(NDPH)

Pathology

Infectious mononucleosis

Epstein–Barr can cause

, also known as 'glandular fever', 'mono' and 'Pfeiffer's disease'. Infectious mononucleosis is caused when a person is first exposed to the virus during or after adolescence. It is predominantly found in the developing world, and most children in the developing world are found to have already been infected by around 18 months of age. Infection of children can occur when adults mouth feed or pre-chew food before giving it to the child. EBV

antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

tests turn up almost universally positive. In the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...

roughly half of five-year-olds have been infected.

EBV-associated malignancies

The strongest evidence linking EBV and cancer formation is found in

and

nasopharyngeal carcinoma Nasopharyngeal carcinoma (NPC), or nasopharynx cancer, is the most common cancer originating in the nasopharynx, most commonly in the postero-lateral nasopharynx or pharyngeal recess ( fossa of Rosenmüller), accounting for 50% of cases. NPC occurs ...

. Additionally, it has been postulated to be a trigger for a subset of

chronic fatigue syndrome Chronic fatigue syndrome (CFS), also called myalgic encephalomyelitis (ME) or ME/CFS, is a complex, debilitating, long-term medical condition. The causes and mechanisms of the disease are not fully understood. Distinguishing core symptoms are ...

patients as well as

and other

autoimmune In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". P ...

diseases.

is a type of

and is most common in

equatorial Africa Equatorial Africa is an ambiguous term that sometimes is used to refer either to the equatorial region of Sub-Saharan Africa traversed by the Equator, more broadly to tropical Africa or in a biological and geo-environmental sense to the intra-tr ...

and is co-existent with the presence of

malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...

. Malaria infection causes reduced immune surveillance of

B cell B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...

s immortalized by EBV, resulting in an excessive number of B cells and an increased likelihood of an unchecked mutation. Repeated mutations can lead to loss of cell-cycle control, causing excessive proliferation observed as Burkitt's lymphoma. Burkitt's lymphoma commonly affects the

jaw bone The jaw is any opposable articulated structure at the entrance of the mouth, typically used for grasping and manipulating food. The term ''jaws'' is also broadly applied to the whole of the structures constituting the vault of the mouth and serv ...

, forming a huge tumor mass. It responds quickly to

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

treatment, namely

cyclophosphamide Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...

, but recurrence is common. Other B cell lymphomas arise in immunocompromised patients such as those with

AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual m ...

or who have undergone organ transplantation with associated

immunosuppression Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse react ...

(Post-Transplant Lymphoproliferative Disorder (PTLPD)).

Smooth muscle Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...

tumors are also associated with the virus in malignant patients.

Nasopharyngeal carcinoma Nasopharyngeal carcinoma (NPC), or nasopharynx cancer, is the most common cancer originating in the nasopharynx, most commonly in the postero-lateral nasopharynx or pharyngeal recess ( fossa of Rosenmüller), accounting for 50% of cases. NPC occurs ...

is a cancer found in the

upper respiratory tract The respiratory tract is the subdivision of the respiratory system involved with the process of respiration in mammals. The respiratory tract is lined with respiratory epithelium as respiratory mucosa. Air is breathed in through the nose to th ...

, most commonly in the

nasopharynx The pharynx (plural: pharynges) is the part of the throat behind the mouth and nasal cavity, and above the oesophagus and trachea (the tubes going down to the stomach and the lungs). It is found in vertebrates and invertebrates, though its struct ...

, and is linked to the EBV virus. It is found predominantly in

Southern China South China () is a geographical and cultural region that covers the southernmost part of China. Its precise meaning varies with context. A notable feature of South China in comparison to the rest of China is that most of its citizens are not n ...

and Africa, due to both genetic and environmental factors. It is much more common in people of Chinese ancestry (genetic), but is also linked to the Chinese diet of a high amount of smoked fish, which contain

nitrosamines In organic chemistry, nitrosamines (or more formally ''N''-Nitrosamines) are organic compounds with the chemical structure , where R is usually an alkyl group. They feature a nitroso group () bonded to a deprotonated amine. Most nitrosamines are ...

, well known

carcinogens A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive substan ...

(environmental).

Diagnosis

EBV can be diagnosed through a

serological test Serology is the scientific study of serum and other body fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection (against a given m ...

which detects

antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

in the blood. A serological test should not be conducted among patients with antibody deficiencies and/or passive antibodies. Another test involves screening for the measurement of EBV viral loads in

peripheral blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...

Radiographic Radiography is an imaging technique using X-rays, gamma rays, or similar ionizing radiation and non-ionizing radiation to view the internal form of an object. Applications of radiography include medical radiography ("diagnostic" and "therapeut ...

testing is often paired with EBV viral load measuring. A

biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...

can also be conducted in order to find where the EBV is manifested.

Treatment

There is no specific treatment for infectious mononucleosis, other than treating the symptoms. In severe cases, steroids such as

corticosteroids Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involve ...

may be used to control the swelling of the throat and tonsils. Currently, there are no antiviral drugs or

vaccines A vaccine is a biological preparation that provides active acquired immunity The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and pro ...

available. It is important to note that symptoms related to infectious mononucleosis caused by EBV infection seldom last for more than 4 months. When such an illness lasts more than 6 months, it is frequently called chronic EBV infection. However, valid laboratory evidence for continued active EBV infection is seldom found in these patients. The illness should be investigated further to determine if it meets the criteria for

, or CFS. This process includes ruling out other causes of chronic illness or fatigue.

References

External links

{{DEFAULTSORT:Epstein-Barr virus infection Epstein–Barr virus–associated diseases