Infectious mononucleosis
Encyclopedia
Infectious mononucleosis (IM; also known as EBV infectious mononucleosis or glandular fever or Pfeiffer's disease or Filatov's disease and sometimes colloquially as the kissing disease from its oral transmission or simply as mono in North America
and as glandular fever in other English-speaking countries) is an infectious, widespread viral disease caused by the Epstein–Barr virus (EBV), one type of herpes virus
, to which more than 90% of adults have been exposed. Occasionally, the symptoms can recur at a later period. Most people are exposed to the virus as children, when the disease produces no noticeable symptoms or only flu-like symptoms. In developing countries, people are exposed to the virus in early childhood more often than in developed countries. As a result, the disease in its observable form is more common in developed countries. It is most common among adolescents and young adults.
Especially in adolescents and young adults, the disease is characterized by fever
, sore throat and fatigue, along with several other possible signs and symptoms. It is primarily diagnosed by observation of symptoms, but suspicion can be confirmed by several diagnostic tests.
The syndrome was described as an infectious process by Nil Filatov in 1887 and independently by Emil Pfeiffer
in 1889.
The classic symptoms of mononucleosis are a sore throat, fever
, fatigue, malaise
, pharyngeal
inflammation, vomiting, petechia
e and loss of appetite. Common signs include lymphadenopathy
(enlarged lymph nodes), splenomegaly
(enlarged spleen
), hepatitis
(refers to inflammation of hepatocytes—cells in the liver) and hemolysis
(the bursting of red blood cell
s). Older adults are less likely to have a sore throat or lymphadenopathy, but are instead more likely to present with hepatomegaly
(enlargement of the liver) and jaundice
. Rarer signs and symptoms include thrombocytopenia
(lower levels of platelet
s), with or without pancytopenia
(lower levels of all types of blood cells), splenic rupture, splenic hemorrhage, upper airway obstruction, pericarditis
and pneumonitis
. Another rare manifestation of mononucleosis is erythema multiforme
.
Mononucleosis is sometimes accompanied by secondary cold agglutinin disease—an autoimmune disease
in which abnormal circulating antibodies directed against red blood cell
s can lead to a form of autoimmune hemolytic anemia
. The cold agglutinin detected is of anti-i
specificity. Patients with infectious mononucleosis are sometimes misdiagnosed with a streptococcal pharyngitis (because of the classical clinical triad of fever, pharyngitis
and adenopathy
) and are given antibiotics such as ampicillin
or amoxicillin
as treatment. Some studies indicate that approximately 80–90% of patients with acute Epstein–Barr virus infection treated with such antibiotics develop a red, diffuse rash.
, but that one gives a negative on the heterophile antibody test. Because of this, some sources say that infectious mononucleosis is caused by the Epstein–Barr virus.
The infection is spread via saliva
and has an incubation period
of 4–7 weeks. Symptoms usually persist for 2–3 weeks, but fatigue is often more prolonged.
How long someone with the virus stays contagious
after symptoms are gone is uncertain, but it is thought that the most contagious period lasts about 6 weeks after the onset of symptoms. Some studies indicate that a person can spread the infection for many months after the symptoms are completely gone, one particular study indicating as long as 18 months.
The virus replicates first within epithelial cell
s in the pharynx
(which causes pharyngitis
, or sore throat), and later primarily within B cell
s (which are invaded via their CD21). The host immune response involves cytotoxic (CD8-positive) T cell
s against infected B lymphocytes, resulting in enlarged atypical lymphocytes (Downey cells
).
When the infection is acute (recent onset, instead of chronic
), heterophile
antibodies are produced.
), while the person also has fever, pharyngitis and adenopathy. Furthermore, it should be confirmed by a serological test
. The atypical lymphocytes resembled monocytes when they were first discovered, thus the term "mononucleosis" was coined. Diagnostic tests are used to confirm infectious mononucleosis but the disease should be suspected from symptoms prior to the results from hematology
. These criteria are specific; however, they are not particularly sensitive
and are more useful for research than for clinical use. Only half the patients presenting with the symptoms held by mononucleosis and a positive heterophile antibody test (monospot test
) meet the entire criteria. One key procedure is to differentiate between infectious mononucleosis and mononucleosis-like symptoms.
There have been few studies on infectious mononucleosis in a primary care environment, the best of which studied 700 patients, of which 15 were found to have mononucleosis upon a heterophile antibody test. More useful in a diagnostic sense are the signs and symptoms themselves. The presence of splenomegaly
, posterior cervical adenopathy, axillary
adenopathy, and inguinal
adenopathy are the most useful to suspect a diagnosis of infectious mononucleosis. On the other hand, the absence of cervical adenopathy and fatigue are the most useful to dismiss the idea of infectious mononucleosis as the correct diagnosis. The insensitivity of the physical examination in detecting splenomegaly
means that it should not be used as evidence against infectious mononucleosis.
In the past the most common test for diagnosing infectious mononucleosis was the heterophile antibody test which involves testing heterophile antibodies by agglutination of guinea pig, sheep and horse red blood cells. As with the aforementioned criteria, this test is specific but not particularly sensitive
(with a false-negative rate of as high as 25% in the first week, 5–10% in the second and 5% in the third). 90% of patients have heterophile antibodies by week 3, disappearing in under a year. The antibodies
involved in the test do not interact with the Epstein–Barr virus or any of its antigen
s. More recently, tests that are more sensitive have been developed such as the Immunoglobulin G
(IgG) and Immunoglobulin M
(IgM) tests. IgG, when positive, reflects a past infection, whereas IgM reflects a current infection. When negative, these tests are more accurate in ruling out infectious mononucleosis. However, when positive, they feature similar sensitivities to the heterophile antibody test. Therefore, these tests are useful for diagnosing infectious mononucleosis in people with highly suggestive symptoms and a negative heterophile antibody test. Another test searches for the Epstein–Barr nuclear antigen, while it is not normally recognizable until several weeks into the disease, and is useful for distinguishing between a recent-onset of infectious mononucleosis and symptoms caused by a previous infection. Elevated hepatic transaminase
levels is highly suggestive of infectious mononucleosis, occurring in up to 50% of patients.
A fibrin ring granuloma
may be present.
infections. These diseases are clinically very similar by their signs and symptoms. Because their management is much the same it is not always helpful, or possible, to distinguish between EBV mononucleosis and cytomegalovirus infection. However, in pregnant women, differentiation of mononucleosis from toxoplasmosis is associated with significant consequences for the fetus
.
Acute HIV infection can mimic signs similar to those of infectious mononucleosis and tests should be performed for pregnant women for the same reason as toxoplasmosis.
Other conditions from which to distinguish infectious mononucleosis include leukemia
, tonsillitis
, diphtheria
, common cold
and influenza
(the flu).
and only symptomatic and/or supportive treatments are used. Rest is recommended during the acute phase of the infection, but activity should be resumed once acute symptoms have resolved. Nevertheless, heavy physical activity and contact sports should be avoided to mitigate the risk of splenic rupture, for at least one month following initial infection or splenomegaly
has resolved, as determined by a treating physician.
s (NSAIDs) like ibuprofen
may be used to reduce fever and pain. Prednisone
, a corticosteroid
, is commonly used as an anti-inflammatory to reduce symptoms of pharyngeal
pain, odynophagia
, or enlarged tonsils, although its use remains controversial due to the rather limited benefit and the potential of side effects. Intravenous corticosteroid
s, usually hydrocortisone or dexamethasone
, are not recommended for routine use but may be useful if there is a risk of airway obstruction, severe thrombocytopenia
, or hemolytic anemia
. There is little evidence to support the use of aciclovir
, although it may reduce initial viral shedding. However, the antiviral drug valacyclovir has recently been shown to lower or eliminate the presence of the Epstein–Barr virus in subjects afflicted with acute mononucleosis, leading to a significant decrease in the severity of symptoms. Although antivirals are not recommended for patients presenting with simple infectious mononucleosis, they may be useful (in conjunction with steroids) in the management of patients with severe EBV manifestations, such as EBV meningitis, peripheral neuritis, hepatitis, or hematologic complications. Antibiotic
s are not used as they are ineffective against viral infections. The antibiotics ampicillin
and later the related amoxicillin
are relatively contraindicated in the case of any coinciding bacterial infections during mononucleosis because their use precipitates a non-allergic rash close to 99% of the time.Yet another reported risk is given in:
*
In a small percentage of cases, mononucleosis infection is complicated by co-infection with streptococcal
infection in the throat and tonsils (strep throat). Penicillin
or other antibiotics (with the exception of the two mentioned above) should be administered to treat the strep throat. Opioid
analgesics are also relatively contraindicated due to risk of respiratory depression.
are uncommon, occurring in less than 5% of cases:
Once the acute symptoms of an initial infection disappear, they often do not return. But once infected, the patient carries the virus for the rest of his or her life. The virus typically lives dormantly in B lymphocytes. Independent infections of mononucleosis may be contracted multiple times, regardless of whether the patient is already carrying the virus dormantly. Periodically, the virus can reactivate, during which time the patient is again infectious, but usually without any symptoms of illness. Usually, a patient has few if any further symptoms or problems from the latent B lymphocyte infection. However, in susceptible hosts under the appropriate environmental stressors the virus can reactivate and cause vague physical symptoms (or may be subclinical), and during this phase the virus can spread to others. Similar reactivation or chronic subclinical viral activity in susceptible hosts may trigger multiple host autoimmune diseases, such as systemic lupus erythematosus
, rheumatoid arthritis
, Sjogren's syndrome
, antiphospholipid antibody syndrome, and multiple sclerosis
. Such chronic immunologic stimulation may also trigger multiple type of cancers, particularly lymphoma—strongest cancer associations with EBV are nasopharyngeal carcinoma
s, Burkitt's lymphoma
, and Hodgkin's lymphoma
. EBV's potential to trigger such a wide range of autoimmune diseases and cancers probably relates to its primary infection of B lymphocytes (the primary antibody-producing cell of the immune system) and ability to alter both lymphocyte proliferation and lymphocyte antibody production.
North America
North America is a continent wholly within the Northern Hemisphere and almost wholly within the Western Hemisphere. It is also considered a northern subcontinent of the Americas...
and as glandular fever in other English-speaking countries) is an infectious, widespread viral disease caused by the Epstein–Barr virus (EBV), one type of herpes virus
Herpesviridae
The Herpesviridae are a large family of DNA viruses that cause diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word herpein , referring to the latent, recurring infections typical of this group of viruses...
, to which more than 90% of adults have been exposed. Occasionally, the symptoms can recur at a later period. Most people are exposed to the virus as children, when the disease produces no noticeable symptoms or only flu-like symptoms. In developing countries, people are exposed to the virus in early childhood more often than in developed countries. As a result, the disease in its observable form is more common in developed countries. It is most common among adolescents and young adults.
Especially in adolescents and young adults, the disease is characterized by fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, sore throat and fatigue, along with several other possible signs and symptoms. It is primarily diagnosed by observation of symptoms, but suspicion can be confirmed by several diagnostic tests.
The syndrome was described as an infectious process by Nil Filatov in 1887 and independently by Emil Pfeiffer
Emil Pfeiffer
Emil Pfeiffer was a German physician and paediatrician.He studied medicine at the universities of Bonn, Würzburg, and Berlin. It was at Berlin where he received his doctorate in 1869....
in 1889.
Signs and symptoms
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, fatigue, malaise
Malaise
Malaise is a feeling of general discomfort or uneasiness, of being "out of sorts", often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell"...
, pharyngeal
Human pharynx
The human pharynx is the part of the throat situated immediately posterior to the mouth and nasal cavity, and anterior to the esophagus and larynx. The human pharynx is conventionally divided into three sections: the nasopharynx , the oropharynx , and the laryngopharynx...
inflammation, vomiting, petechia
Petechia
A petechia is a small red or purple spot on the body, caused by a minor hemorrhage ."Petechiae" refers to one of the three major classes of purpuric skin conditions. Purpuric eruptions are classified by size into three broad categories...
e and loss of appetite. Common signs include lymphadenopathy
Lymphadenopathy
Lymphadenopathy is a term meaning "disease of the lymph nodes." It is, however, almost synonymously used with "swollen/enlarged lymph nodes". It could be due to infection, auto-immune disease, or malignancy....
(enlarged lymph nodes), splenomegaly
Splenomegaly
Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant of the human abdomen. It is one of the four cardinal signs of hypersplenism, some reduction in the number of circulating blood cells affecting granulocytes, erythrocytes or platelets in any...
(enlarged spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
), hepatitis
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
(refers to inflammation of hepatocytes—cells in the liver) and hemolysis
Hemolysis
Hemolysis —from the Greek meaning "blood" and meaning a "loosing", "setting free" or "releasing"—is the rupturing of erythrocytes and the release of their contents into surrounding fluid...
(the bursting of red blood cell
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
s). Older adults are less likely to have a sore throat or lymphadenopathy, but are instead more likely to present with hepatomegaly
Hepatomegaly
Hepatomegaly is the condition of having an enlarged liver. It is a nonspecific medical sign having many causes, which can broadly be broken down into infection, direct toxicity, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdominal mass...
(enlargement of the liver) and jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
. Rarer signs and symptoms include thrombocytopenia
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
(lower levels of platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
s), with or without pancytopenia
Pancytopenia
Pancytopenia is a medical condition in which there is a reduction in the number of red and white blood cells, as well as platelets.If only two parameters from the full blood count are low, the term bicytopenia can be used...
(lower levels of all types of blood cells), splenic rupture, splenic hemorrhage, upper airway obstruction, pericarditis
Pericarditis
Pericarditis is an inflammation of the pericardium . A characteristic chest pain is often present.The causes of pericarditis are varied, including viral infections of the pericardium, idiopathic causes, uremic pericarditis, bacterial infections of the precardium Pericarditis is an inflammation of...
and pneumonitis
Pneumonitis
Pneumonitis or pulmonitis is a general term that refers to inflammation of lung tissue.Pneumonia is pneumonitis combined with consolidation and exudation...
. Another rare manifestation of mononucleosis is erythema multiforme
Erythema multiforme
Erythema multiforme is a skin condition of unknown cause, possibly mediated by deposition of immune complex in the superficial microvasculature of the skin and oral mucous membrane that usually follows an infection or drug exposure...
.
Mononucleosis is sometimes accompanied by secondary cold agglutinin disease—an autoimmune disease
Autoimmune disease
Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...
in which abnormal circulating antibodies directed against red blood cell
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
s can lead to a form of autoimmune hemolytic anemia
Autoimmune hemolytic anemia
Autoimmune hemolytic anemia occurs when antibodies directed against the person's own red blood cells cause the RBCs to burst , leading to insufficient plasma concentration. The lifetime of the RBCs is reduced from the normal 100–120 days to just a few days in serious cases...
. The cold agglutinin detected is of anti-i
Ii antigen system
Ii antigen system is a human blood group system based upon genes on chromosome 6.-External links:* at BGMUT Blood Group Antigen Gene Mutation Database at NCBI, NIH...
specificity. Patients with infectious mononucleosis are sometimes misdiagnosed with a streptococcal pharyngitis (because of the classical clinical triad of fever, pharyngitis
Pharyngitis
Pharyngitis is an inflammation of the throat or pharynx. In most cases it is quite painful, and is the most common cause of a sore throat.Like many types of inflammation, pharyngitis can be acute – characterized by a rapid onset and typically a relatively short course – or chronic....
and adenopathy
Lymphadenopathy
Lymphadenopathy is a term meaning "disease of the lymph nodes." It is, however, almost synonymously used with "swollen/enlarged lymph nodes". It could be due to infection, auto-immune disease, or malignancy....
) and are given antibiotics such as ampicillin
Ampicillin
Ampicillin is a beta-lactam antibiotic that has been used extensively to treat bacterial infections since 1961. Until the introduction of ampicillin by the British company Beecham, penicillin therapies had only been effective against Gram-positive organisms such as staphylococci and streptococci...
or amoxicillin
Amoxicillin
Amoxicillin , formerly amoxycillin , and abbreviated amox, is a moderate-spectrum, bacteriolytic, β-lactam antibiotic used to treat bacterial infections caused by susceptible microorganisms. It is usually the drug of choice within the class because it is better absorbed, following oral...
as treatment. Some studies indicate that approximately 80–90% of patients with acute Epstein–Barr virus infection treated with such antibiotics develop a red, diffuse rash.
Pathophysiology
Infectious mononucleosis occurs with infection by the Epstein–Barr virus. A similar condition can be caused by cytomegalovirusCytomegalovirus
Cytomegalovirus is a viral genus of the viral group known as Herpesviridae or herpesviruses. It is typically abbreviated as CMV: The species that infects humans is commonly known as human CMV or human herpesvirus-5 , and is the most studied of all cytomegaloviruses...
, but that one gives a negative on the heterophile antibody test. Because of this, some sources say that infectious mononucleosis is caused by the Epstein–Barr virus.
The infection is spread via saliva
Saliva
Saliva , referred to in various contexts as spit, spittle, drivel, drool, or slobber, is the watery substance produced in the mouths of humans and most other animals. Saliva is a component of oral fluid. In mammals, saliva is produced in and secreted from the three pairs of major salivary glands,...
and has an incubation period
Incubation period
Incubation period is the time elapsed between exposure to a pathogenic organism, a chemical or radiation, and when symptoms and signs are first apparent...
of 4–7 weeks. Symptoms usually persist for 2–3 weeks, but fatigue is often more prolonged.
How long someone with the virus stays contagious
Contagious disease
A contagious disease is a subset category of infectious diseases , which are easily transmitted by physical contact with the person suffering the disease, or by their secretions or objects touched by them....
after symptoms are gone is uncertain, but it is thought that the most contagious period lasts about 6 weeks after the onset of symptoms. Some studies indicate that a person can spread the infection for many months after the symptoms are completely gone, one particular study indicating as long as 18 months.
The virus replicates first within epithelial cell
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
s in the pharynx
Human pharynx
The human pharynx is the part of the throat situated immediately posterior to the mouth and nasal cavity, and anterior to the esophagus and larynx. The human pharynx is conventionally divided into three sections: the nasopharynx , the oropharynx , and the laryngopharynx...
(which causes pharyngitis
Pharyngitis
Pharyngitis is an inflammation of the throat or pharynx. In most cases it is quite painful, and is the most common cause of a sore throat.Like many types of inflammation, pharyngitis can be acute – characterized by a rapid onset and typically a relatively short course – or chronic....
, or sore throat), and later primarily within B cell
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
s (which are invaded via their CD21). The host immune response involves cytotoxic (CD8-positive) T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
s against infected B lymphocytes, resulting in enlarged atypical lymphocytes (Downey cells
Reactive lymphocyte
Reactive lymphocytes are lymphocytes that become large as a result of antigen stimulation. Typically they can be more than 30 µm in diameter with varying size and shape....
).
When the infection is acute (recent onset, instead of chronic
Chronic (medicine)
A chronic disease is a disease or other human health condition that is persistent or long-lasting in nature. The term chronic is usually applied when the course of the disease lasts for more than three months. Common chronic diseases include asthma, cancer, diabetes and HIV/AIDS.In medicine, the...
), heterophile
Heterophile
Heterophile is an alternate term to heterosexual and once competed with it for currency, but only did so successfully in Scandinavia. It is a parallel concept to homophile....
antibodies are produced.
Diagnosis
The most commonly used diagnostic criterion is the presence of 50% lymphocytes with at least 10% atypical lymphocytes (large, irregular nucleiCell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
), while the person also has fever, pharyngitis and adenopathy. Furthermore, it should be confirmed by a serological test
Serology
Serology is the scientific study of blood serum and other bodily fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum...
. The atypical lymphocytes resembled monocytes when they were first discovered, thus the term "mononucleosis" was coined. Diagnostic tests are used to confirm infectious mononucleosis but the disease should be suspected from symptoms prior to the results from hematology
Hematology
Hematology, also spelled haematology , is the branch of biology physiology, internal medicine, pathology, clinical laboratory work, and pediatrics that is concerned with the study of blood, the blood-forming organs, and blood diseases...
. These criteria are specific; however, they are not particularly sensitive
Sensitivity and specificity
Sensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...
and are more useful for research than for clinical use. Only half the patients presenting with the symptoms held by mononucleosis and a positive heterophile antibody test (monospot test
Monospot test
The test is sensitive for heterophile antibodies produced by the human immune system in response to EBV infection.The monospot test, a form of the heterophile antibody test, is a rapid test for infectious mononucleosis due to Epstein–Barr virus . Commercially-available test kits are 70-92%...
) meet the entire criteria. One key procedure is to differentiate between infectious mononucleosis and mononucleosis-like symptoms.
There have been few studies on infectious mononucleosis in a primary care environment, the best of which studied 700 patients, of which 15 were found to have mononucleosis upon a heterophile antibody test. More useful in a diagnostic sense are the signs and symptoms themselves. The presence of splenomegaly
Splenomegaly
Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant of the human abdomen. It is one of the four cardinal signs of hypersplenism, some reduction in the number of circulating blood cells affecting granulocytes, erythrocytes or platelets in any...
, posterior cervical adenopathy, axillary
Axillary
Axillary means "related to the axilla "."Axillary" may refer to:* Axillary artery* Axillary vein* Axillary nerve* Axillary bud...
adenopathy, and inguinal
Inguinal
In human anatomy, the inguinal region refers to either the groin or the lower lateral regions of the abdomen. It may also refer to:* Conjoint tendon, previously known as the inguinal aponeurotic falx, a structure formed from the transversus abdominis insertion into the pecten pubis* Granuloma...
adenopathy are the most useful to suspect a diagnosis of infectious mononucleosis. On the other hand, the absence of cervical adenopathy and fatigue are the most useful to dismiss the idea of infectious mononucleosis as the correct diagnosis. The insensitivity of the physical examination in detecting splenomegaly
Splenomegaly
Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant of the human abdomen. It is one of the four cardinal signs of hypersplenism, some reduction in the number of circulating blood cells affecting granulocytes, erythrocytes or platelets in any...
means that it should not be used as evidence against infectious mononucleosis.
In the past the most common test for diagnosing infectious mononucleosis was the heterophile antibody test which involves testing heterophile antibodies by agglutination of guinea pig, sheep and horse red blood cells. As with the aforementioned criteria, this test is specific but not particularly sensitive
Sensitivity and specificity
Sensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...
(with a false-negative rate of as high as 25% in the first week, 5–10% in the second and 5% in the third). 90% of patients have heterophile antibodies by week 3, disappearing in under a year. The antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
involved in the test do not interact with the Epstein–Barr virus or any of its antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
s. More recently, tests that are more sensitive have been developed such as the Immunoglobulin G
Immunoglobulin G
Immunoglobulin G are antibody molecules. Each IgG is composed of four peptide chains — two heavy chains γ and two light chains. Each IgG has two antigen binding sites. Other immunoglobulins may be described in terms of polymers with the IgG structure considered the monomer.IgG constitutes 75%...
(IgG) and Immunoglobulin M
Immunoglobulin M
Immunoglobulin M, or IgM for short, is a basic antibody that is produced by B cells. It is the primary antibody against A and B antigens on red blood cells. IgM is by far the physically largest antibody in the human circulatory system...
(IgM) tests. IgG, when positive, reflects a past infection, whereas IgM reflects a current infection. When negative, these tests are more accurate in ruling out infectious mononucleosis. However, when positive, they feature similar sensitivities to the heterophile antibody test. Therefore, these tests are useful for diagnosing infectious mononucleosis in people with highly suggestive symptoms and a negative heterophile antibody test. Another test searches for the Epstein–Barr nuclear antigen, while it is not normally recognizable until several weeks into the disease, and is useful for distinguishing between a recent-onset of infectious mononucleosis and symptoms caused by a previous infection. Elevated hepatic transaminase
Transaminase
In biochemistry, a transaminase or an aminotransferase is an enzyme that catalyzes a type of reaction between an amino acid and an α-keto acid. To be specific, this reaction involves removing the amino group from the amino acid, leaving behind an α-keto acid, and transferring it to the...
levels is highly suggestive of infectious mononucleosis, occurring in up to 50% of patients.
A fibrin ring granuloma
Fibrin ring granuloma
A fibrin ring granuloma is a histopathological finding that is characteristic of Q fever. On hematoxylin-eosin staining, the fibrin ring granuloma consists of a central lipid vacuole surrounded by a dense red fibrin ring and epithelioid macrophages...
may be present.
Differential diagnosis
Diagnosis of acute infectious mononucleosis should also take into consideration acute cytomegalovirus infection and Toxoplasma gondiiToxoplasma gondii
Toxoplasma gondii is a species of parasitic protozoa in the genus Toxoplasma. The definitive host of T. gondii is the cat, but the parasite can be carried by many warm-blooded animals . Toxoplasmosis, the disease of which T...
infections. These diseases are clinically very similar by their signs and symptoms. Because their management is much the same it is not always helpful, or possible, to distinguish between EBV mononucleosis and cytomegalovirus infection. However, in pregnant women, differentiation of mononucleosis from toxoplasmosis is associated with significant consequences for the fetus
Fetus
A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...
.
Acute HIV infection can mimic signs similar to those of infectious mononucleosis and tests should be performed for pregnant women for the same reason as toxoplasmosis.
Other conditions from which to distinguish infectious mononucleosis include leukemia
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
, tonsillitis
Tonsillitis
Tonsillitis is an inflammation of the tonsils most commonly caused by viral or bacterial infection. Symptoms of tonsillitis include sore throat and fever. While no treatment has been found to shorten the duration of viral tonsillitis, bacterial causes are treatable with antibiotics...
, diphtheria
Diphtheria
Diphtheria is an upper respiratory tract illness caused by Corynebacterium diphtheriae, a facultative anaerobic, Gram-positive bacterium. It is characterized by sore throat, low fever, and an adherent membrane on the tonsils, pharynx, and/or nasal cavity...
, common cold
Common cold
The common cold is a viral infectious disease of the upper respiratory system, caused primarily by rhinoviruses and coronaviruses. Common symptoms include a cough, sore throat, runny nose, and fever...
and influenza
Influenza
Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...
(the flu).
Self care
Infectious mononucleosis is generally self-limitingSelf-limiting (biology)
In biology, a self-limiting organism or colony of organisms limits its own growth by its actions. For example, a single organism may have a maximum size determined by genetics, or a colony of organisms may release waste which is ultimately toxic to the colony once it exceeds a certain population...
and only symptomatic and/or supportive treatments are used. Rest is recommended during the acute phase of the infection, but activity should be resumed once acute symptoms have resolved. Nevertheless, heavy physical activity and contact sports should be avoided to mitigate the risk of splenic rupture, for at least one month following initial infection or splenomegaly
Splenomegaly
Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant of the human abdomen. It is one of the four cardinal signs of hypersplenism, some reduction in the number of circulating blood cells affecting granulocytes, erythrocytes or platelets in any...
has resolved, as determined by a treating physician.
Medications
In terms of pharmacotherapies, non-steroidal anti-inflammatory drugNon-steroidal anti-inflammatory drug
Nonsteroidal anti-inflammatory drugs, usually abbreviated to NSAIDs or NAIDs, but also referred to as nonsteroidal anti-inflammatory agents/analgesics or nonsteroidal Anti-inflammatory medicines , are drugs with analgesic and antipyretic effects and which have, in higher doses, anti-inflammatory...
s (NSAIDs) like ibuprofen
Ibuprofen
Ibuprofen is a nonsteroidal anti-inflammatory drug used for relief of symptoms of arthritis, fever, as an analgesic , especially where there is an inflammatory component, and dysmenorrhea....
may be used to reduce fever and pain. Prednisone
Prednisone
Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects...
, a corticosteroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
, is commonly used as an anti-inflammatory to reduce symptoms of pharyngeal
Human pharynx
The human pharynx is the part of the throat situated immediately posterior to the mouth and nasal cavity, and anterior to the esophagus and larynx. The human pharynx is conventionally divided into three sections: the nasopharynx , the oropharynx , and the laryngopharynx...
pain, odynophagia
Odynophagia
Odynophagia is painful swallowing, in the mouth or esophagus. It can occur with or without dysphagia, or difficult swallowing....
, or enlarged tonsils, although its use remains controversial due to the rather limited benefit and the potential of side effects. Intravenous corticosteroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
s, usually hydrocortisone or dexamethasone
Dexamethasone
Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid drugs. It acts as an anti-inflammatory and immunosuppressant...
, are not recommended for routine use but may be useful if there is a risk of airway obstruction, severe thrombocytopenia
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
, or hemolytic anemia
Hemolytic anemia
Hemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells , either in the blood vessels or elsewhere in the human body . It has numerous possible causes, ranging from relatively harmless to life-threatening...
. There is little evidence to support the use of aciclovir
Aciclovir
Aciclovir or acyclovir , chemical name acycloguanosine, abbreviated as ACV,is a guanosine analogue antiviral drug, marketed under trade names such as Cyclovir, Herpex, Acivir, Acivirax, Zovirax, and Zovir...
, although it may reduce initial viral shedding. However, the antiviral drug valacyclovir has recently been shown to lower or eliminate the presence of the Epstein–Barr virus in subjects afflicted with acute mononucleosis, leading to a significant decrease in the severity of symptoms. Although antivirals are not recommended for patients presenting with simple infectious mononucleosis, they may be useful (in conjunction with steroids) in the management of patients with severe EBV manifestations, such as EBV meningitis, peripheral neuritis, hepatitis, or hematologic complications. Antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
s are not used as they are ineffective against viral infections. The antibiotics ampicillin
Ampicillin
Ampicillin is a beta-lactam antibiotic that has been used extensively to treat bacterial infections since 1961. Until the introduction of ampicillin by the British company Beecham, penicillin therapies had only been effective against Gram-positive organisms such as staphylococci and streptococci...
and later the related amoxicillin
Amoxicillin
Amoxicillin , formerly amoxycillin , and abbreviated amox, is a moderate-spectrum, bacteriolytic, β-lactam antibiotic used to treat bacterial infections caused by susceptible microorganisms. It is usually the drug of choice within the class because it is better absorbed, following oral...
are relatively contraindicated in the case of any coinciding bacterial infections during mononucleosis because their use precipitates a non-allergic rash close to 99% of the time.Yet another reported risk is given in:
*
In a small percentage of cases, mononucleosis infection is complicated by co-infection with streptococcal
Streptococcus
Streptococcus is a genus of spherical Gram-positive bacteria belonging to the phylum Firmicutes and the lactic acid bacteria group. Cellular division occurs along a single axis in these bacteria, and thus they grow in chains or pairs, hence the name — from Greek στρεπτος streptos, meaning...
infection in the throat and tonsils (strep throat). Penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....
or other antibiotics (with the exception of the two mentioned above) should be administered to treat the strep throat. Opioid
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
analgesics are also relatively contraindicated due to risk of respiratory depression.
Prognosis
Serious complicationsComplication (medicine)
Complication, in medicine, is an unfavorable evolution of a disease, a health condition or a medical treatment. The disease can become worse in its severity or show a higher number of signs, symptoms or new pathological changes, become widespread throughout the body or affect other organ systems. A...
are uncommon, occurring in less than 5% of cases:
- CNSCentral nervous systemThe central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
: MeningitisMeningitisMeningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...
, encephalitisEncephalitisEncephalitis is an acute inflammation of the brain. Encephalitis with meningitis is known as meningoencephalitis. Symptoms include headache, fever, confusion, drowsiness, and fatigue...
, hemiplegiaHemiplegiaHemiplegia /he.mə.pliː.dʒiə/ is total paralysis of the arm, leg, and trunk on the same side of the body. Hemiplegia is more severe than hemiparesis, wherein one half of the body has less marked weakness....
, Guillain-Barré syndromeGuillain-Barré syndromeGuillain–Barré syndrome , sometimes called Landry's paralysis, is an acute inflammatory demyelinating polyneuropathy , a disorder affecting the peripheral nervous system. Ascending paralysis, weakness beginning in the feet and hands and migrating towards the trunk, is the most typical symptom...
, and transverse myelitisTransverse myelitisTransverse myelitis is a neurological disorder caused by an inflammatory process of the spinal cord, and can cause axonal demyelination. The name is derived from Greek referring to the "spinal cord", and the suffix -itis, which denotes inflammation...
. EBV infection has also been proposed as a risk factor for the development of multiple sclerosisMultiple sclerosisMultiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
(MS), but this has not been confirmed. - HematologicHematologyHematology, also spelled haematology , is the branch of biology physiology, internal medicine, pathology, clinical laboratory work, and pediatrics that is concerned with the study of blood, the blood-forming organs, and blood diseases...
: Hemolytic anemiaAutoimmune hemolytic anemiaAutoimmune hemolytic anemia occurs when antibodies directed against the person's own red blood cells cause the RBCs to burst , leading to insufficient plasma concentration. The lifetime of the RBCs is reduced from the normal 100–120 days to just a few days in serious cases...
(direct Coombs testCoombs testCoombs test refers to two clinical blood tests used in immunohematology and immunology...
is positive) and various cytopeniaCytopeniaCytopenia is a reduction in the number of blood cells. It takes a number of forms:*Low red blood cell count: resulting in anemia.*Low white blood cell count: leukopenia or neutropenia .*Low platelet count: thrombocytopenia.*Low granulocyte count: granulocytopenia*Low red blood...
s; Bleeding (caused by thrombocytopeniaThrombocytopeniaThrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
). - Mild jaundiceJaundiceJaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
- HepatitisHepatitisHepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
(rare) - Upper airway obstruction (tonsillar hypertrophy) (rare)
- FulminantFulminantFulminant is any event or process that occurs suddenly and quickly, and is intense and severe to the point of lethality, i.e., it has an explosive character. The word comes from Latin fulmināre, to strike with lightning...
disease course (immunocompromisedImmunodeficiencyImmunodeficiency is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. Immunodeficiency may also decrease cancer immunosurveillance. Most cases of immunodeficiency are acquired but some people are born with defects in their immune system,...
patients) (rare) - Splenic rupture (rare)
- MyocarditisMyocarditisMyocarditis is inflammation of heart muscle . It resembles a heart attack but coronary arteries are not blocked.Myocarditis is most often due to infection by common viruses, such as parvovirus B19, less commonly non-viral pathogens such as Borrelia burgdorferi or Trypanosoma cruzi, or as a...
and pericarditisPericarditisPericarditis is an inflammation of the pericardium . A characteristic chest pain is often present.The causes of pericarditis are varied, including viral infections of the pericardium, idiopathic causes, uremic pericarditis, bacterial infections of the precardium Pericarditis is an inflammation of...
(rare)
Once the acute symptoms of an initial infection disappear, they often do not return. But once infected, the patient carries the virus for the rest of his or her life. The virus typically lives dormantly in B lymphocytes. Independent infections of mononucleosis may be contracted multiple times, regardless of whether the patient is already carrying the virus dormantly. Periodically, the virus can reactivate, during which time the patient is again infectious, but usually without any symptoms of illness. Usually, a patient has few if any further symptoms or problems from the latent B lymphocyte infection. However, in susceptible hosts under the appropriate environmental stressors the virus can reactivate and cause vague physical symptoms (or may be subclinical), and during this phase the virus can spread to others. Similar reactivation or chronic subclinical viral activity in susceptible hosts may trigger multiple host autoimmune diseases, such as systemic lupus erythematosus
Systemic lupus erythematosus
Systemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...
, rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
, Sjogren's syndrome
Sjögren's syndrome
Sjögren's syndrome , also known as "Mikulicz disease" and "Sicca syndrome", is a systemic autoimmune disease in which immune cells attack and destroy the exocrine glands that produce tears and saliva....
, antiphospholipid antibody syndrome, and multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
. Such chronic immunologic stimulation may also trigger multiple type of cancers, particularly lymphoma—strongest cancer associations with EBV are nasopharyngeal carcinoma
Nasopharyngeal carcinoma
Nasopharyngeal carcinoma is the most common cancer originating in the nasopharynx, the uppermost region of the pharynx , behind the nose where the nasal passages and auditory tubes join the remainder of the upper respiratory tract. NPC differs significantly from other cancers of the head and neck...
s, Burkitt's lymphoma
Burkitt's lymphoma
Burkitt's lymphoma is a cancer of the lymphatic system...
, and Hodgkin's lymphoma
Hodgkin's lymphoma
Hodgkin's lymphoma, previously known as Hodgkin's disease, is a type of lymphoma, which is a cancer originating from white blood cells called lymphocytes...
. EBV's potential to trigger such a wide range of autoimmune diseases and cancers probably relates to its primary infection of B lymphocytes (the primary antibody-producing cell of the immune system) and ability to alter both lymphocyte proliferation and lymphocyte antibody production.