Infectious mononucleosis (IM, mono), also known as glandular fever, is an infection usually caused by the
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).
[ Most people are infected by the virus as children, when the disease produces few or no symptoms.][ In young adults, the disease often results in ]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, enlarged lymph nodes
Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In cl ...
in the neck, and tiredness.[ Most people recover in two to four weeks; however, feeling tired may last for months.][ The ]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 ...
or 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 . may also become swollen,[ and in less than one percent of cases ]splenic rupture
A splenic injury, which includes a ruptured spleen, is any injury to the spleen. The rupture of a normal spleen can be caused by trauma, such as a traffic collision.
Signs and symptoms
In minor injuries with little bleeding, there may be abdomin ...
may occur.
While usually caused by the Epstein–Barr virus, also known as human herpesvirus 4, which is a member of the herpesvirus family,[ a few other viruses may also cause the disease.] It is primarily spread through saliva
Saliva (commonly referred to as spit) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DNA can be ...
but can rarely be spread through semen
Semen, also known as seminal fluid, is an organic bodily fluid created to contain spermatozoa. It is secreted by the gonads (sexual glands) and other sexual organs of male or hermaphroditic animals and can fertilize the female ovum. Semen i ...
or 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 ...
.[ Spread may occur by objects such as drinking glasses or toothbrushes or through a cough or sneeze.][ Those who are infected can spread the disease weeks before symptoms develop.][ Mono is primarily diagnosed based on the symptoms and can be confirmed with blood tests for specific ]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 ...
.[ Another typical finding is ]increased blood lymphocytes
Lymphocytosis is an increase in the number or proportion of lymphocytes in the blood. Absolute lymphocytosis is the condition where there is an increase in the lymphocyte count beyond the normal range while relative lymphocytosis refers to the cond ...
of which more than 10% are atypical.[ The ]monospot
The mononuclear spot test or monospot test, a form of the heterophile antibody test, is a rapid test for infectious mononucleosis due to Epstein–Barr virus (EBV). It is an improvement on the Paul–Bunnell test. The test is specific for heterop ...
test is not recommended for general use due to poor accuracy.
There is no vaccine
A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifie ...
for EBV, though promising vaccine research results exist. Infection can be prevented by not sharing personal items or saliva with an infected person.[ Mono generally improves without any specific treatment.][ Symptoms may be reduced by drinking enough fluids, getting sufficient rest, and taking ]pain medications
An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...
such as paracetamol
Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol.
At a standard dose, paracetamol only slightly decreases body temperature; it is inferior ...
(acetaminophen) and ibuprofen
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used for treating pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus arte ...
.
Mononucleosis most commonly affects those between the ages of 15 to 24 years in the developed world
A developed country (or industrialized country, high-income country, more economically developed country (MEDC), advanced country) is a sovereign state that has a high quality of life, developed economy and advanced technological infrastruct ...
.[ In the ]developing world
A developing country is a sovereign state with a lesser developed industrial base and a lower Human Development Index (HDI) relative to other countries. However, this definition is not universally agreed upon. There is also no clear agreem ...
, people are more often infected in early childhood when there are fewer symptoms. In those between 16 and 20 it is the cause of about 8% of sore throats. About 45 out of 100,000 people develop infectious mono each year in the United States.[ Nearly 95% of people have had an EBV infection by the time they are adults.] The disease occurs equally at all times of the year.[ Mononucleosis was first described in the 1920s and is colloquially known as "the kissing disease".]
Signs and symptoms
The sign
A sign is an object, quality, event, or entity whose presence or occurrence indicates the probable presence or occurrence of something else. A natural sign bears a causal relation to its object—for instance, thunder is a sign of storm, or me ...
s and symptoms
Signs and symptoms are the observed or detectable signs, and experienced symptoms of an disease, illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormali ...
of infectious mononucleosis vary with age.
Children
Before puberty, the disease typically only produces flu
Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptom ...
-like symptoms, if any at all. When found, symptoms tend to be similar to those of common throat infections (mild pharyngitis
Pharyngitis is inflammation of the back of the throat, known as the pharynx. It typically results in a sore throat and fever. Other symptoms may include a Rhinorrhea, runny nose, cough, headache, difficulty swallowing, swollen lymph nodes, and a ...
, with or without tonsillitis
Tonsillitis is inflammation of the tonsils in the upper part of the throat. It can be acute or chronic. Acute tonsillitis typically has a rapid onset. Symptoms may include sore throat, fever, enlargement of the tonsils, trouble swallowing, and en ...
).[
]
Adolescents and young adults
In adolescence
Adolescence () is a transitional stage of physical and psychological development that generally occurs during the period from puberty to adulthood (typically corresponding to the age of majority). Adolescence is usually associated with the t ...
and young adulthood, the disease presents with a characteristic triad:
* 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 ...
– usually lasting 14 days; often mild[
* ]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 ...
– usually severe for 3–5 days, before resolving in the next 7–10 days.
* Swollen glands – mobile; usually located around the back of the neck (posterior cervical lymph nodes
Cervical lymph nodes are lymph nodes found in the neck. Of the 800 lymph nodes in the human body, 300 are in the neck. Cervical lymph nodes are subject to a number of different pathological conditions including tumours, infection and inflammati ...
) and sometimes throughout the body.
Another major symptom is feeling tired.[ ]Headache
Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches.
Headaches can occur as a result ...
s are common, and abdominal pain
Abdominal pain, also known as a stomach ache, is a symptom
Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than ...
s with nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
or vomiting
Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose.
Vomiting can be the result of ailments like Food-poisoning, foo ...
sometimes also occur.[ Symptoms most often disappear after about 2–4 weeks.][ However, fatigue and a general feeling of being unwell (]malaise
As a medical term, malaise is a feeling of general discomfort, uneasiness or lack of wellbeing and often the first sign of an infection or other disease. The word has existed in French since at least the 12th century.
The term is often used ...
) may sometimes last for months.[ Fatigue lasts more than one month in an estimated 28% of cases. Mild fever, swollen neck glands and body aches may also persist beyond 4 weeks.][ Most people are able to resume their usual activities within 2–3 months.][
The most prominent sign of the disease is often the ]pharyngitis
Pharyngitis is inflammation of the back of the throat, known as the pharynx. It typically results in a sore throat and fever. Other symptoms may include a Rhinorrhea, runny nose, cough, headache, difficulty swallowing, swollen lymph nodes, and a ...
, which is frequently accompanied by enlarged tonsils with pus
Pus is an exudate, typically white-yellow, yellow, or yellow-brown, formed at the site of inflammation during bacterial or fungal infection. An accumulation of pus in an enclosed tissue space is known as an abscess, whereas a visible collection ...
—an exudate
An exudate is a fluid emitted by an organism through pores or a wound, a process known as exuding or exudation.
''Exudate'' is derived from ''exude'' 'to ooze' from Latin ''exsūdāre'' 'to (ooze out) sweat' (''ex-'' 'out' and ''sūdāre'' 'to ...
similar to that seen in cases of strep throat
Streptococcal pharyngitis, also known as streptococcal sore throat (strep throat), is pharyngitis (an infection of the pharynx, the back of the throat) caused by ''Streptococcus pyogenes'' a gram-positive, group A streptococcus. Common symptom ...
.[ In about 50% of cases, small reddish-purple spots called ]petechia
A petechia () is a small red or purple spot (≤4 mm in diameter) that can appear on the skin, conjunctiva, retina, and Mucous membrane, mucous membranes which is caused by haemorrhage of capillaries. The word is derived from Italian , 'freckle,' ...
e can be seen on the roof of the mouth. Palatal enanthem
Enanthem or enanthema is a rash (small spots) on the mucous membranes. It is characteristic of patients with viral infections causing Hand, foot, and mouth disease, hand foot and mouth disease, measles, and sometimes chicken pox, or COVID-19. In ...
can also occur, but is relatively uncommon.[
A small minority of people spontaneously present a ]rash
A rash is a change of the human skin which affects its color, appearance, or texture.
A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cr ...
, usually on the arms or trunk, which can be macular
A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this ...
(morbilliform The term morbilliform refers to a rash that looks like measles. The rash consists of macular lesions that are red and usually 2–10 mm in diameter but may be confluent in places. A morbilliform rash is a rose-red flat ( macular) or slightly ...
) or papular
A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this ...
.[ Almost all people given ]amoxicillin
Amoxicillin is an antibiotic medication used to treat a number of bacterial infections. These include middle ear infection, strep throat, pneumonia, skin infections, and urinary tract infections among others. It is taken by mouth, or less c ...
or ampicillin
Ampicillin is an antibiotic used to prevent and treat a number of bacterial infections, such as respiratory tract infections, urinary tract infections, meningitis, salmonellosis, and endocarditis. It may also be used to prevent group B strepto ...
eventually develop a generalized, itchy maculopapular rash, which however does not imply that the person will have adverse reactions to penicillin
Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from ''Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum using ...
s again in the future. Occasional cases of erythema nodosum
Erythema nodosum (EN) is an inflammatory condition characterized by inflammation of the fat cells under the skin, resulting in tender red nodules or lumps that are usually seen on both shins. It can be caused by a variety of conditions, and typi ...
and erythema multiforme
Erythema multiforme (EM) is a skin condition that appears with red patches evolving into target lesions, typically on both hands.
It is a type of erythema possibly mediated by deposition of immune complexes (mostly IgM-bound complexes) in the s ...
have been reported.[ Seizures may also occasionally occur.
]
Complications
Spleen enlargement is common in the second and third weeks, although this may not be apparent on physical examination
In a physical examination, medical examination, or clinical examination, a medical practitioner examines a patient for any possible medical signs or symptoms of a medical condition. It generally consists of a series of questions about the patien ...
. Rarely the spleen may rupture. There may also be some enlargement of the liver.[ ]Jaundice
Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...
occurs only occasionally.[
It generally gets better on its own in people who are otherwise healthy.] When caused by EBV, infectious mononucleosis is classified as one of the Epstein-Barr virus-associated lymphoproliferative diseases. Occasionally the disease may persist and result in a chronic infection. This may develop into systemic EBV-positive T cell lymphoma
Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlar ...
.
Older adults
Infectious mononucleosis mainly affects younger adults.[ When older adults do catch the disease, they less often have characteristic signs and symptoms such as the sore throat and lymphadenopathy.][ Instead, they may primarily experience prolonged fever, fatigue, malaise and body pains.][ They are more likely to have liver enlargement and ]jaundice
Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...
.[ People over 40 years of age are more likely to develop serious illness.][ (See ]Prognosis
Prognosis (Greek: πρόγνωσις "fore-knowing, foreseeing") is a medical term for predicting the likely or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) or remain stabl ...
.)
Incubation period
The exact length of time between infection and symptoms is unclear. A review of the literature made an estimate of 33–49 days. In adolescents and young adults, symptoms are thought to appear around 4–6 weeks after initial infection. Onset is often gradual, though it can be abrupt. The main symptoms may be preceded by 1–2 weeks of fatigue, feeling unwell and body aches.[
]
Cause
Epstein–Barr virus
About 90% of cases of infectious mononucleosis are caused by the 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 ...
, a member of the Herpesviridae
''Herpesviridae'' is a large family of DNA viruses that cause infections and certain diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word ''ἕρπει ...
family of DNA viruses
A DNA virus is a virus that has a genome made of deoxyribonucleic acid (DNA) that is replicated by a DNA polymerase. They can be divided between those that have two strands of DNA in their genome, called double-stranded DNA (dsDNA) viruses, and ...
. It is one of the most commonly found viruses
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsky's 1 ...
throughout the world. Contrary to common belief, the Epstein–Barr virus is not highly contagious. It can only be contracted through direct contact with an infected person's saliva
Saliva (commonly referred to as spit) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DNA can be ...
, such as through kissing or sharing toothbrushes. About 95% of the population has been exposed to this virus by the age of 40, but only 15–20% of teenagers and about 40% of exposed adults actually become infected.
Cytomegalovirus
About 5% to 7% of cases of infectious mononucleosis is caused by human cytomegalovirus
''Human betaherpesvirus 5'', also called human cytomegalovirus (HCMV), is species of virus in the genus ''Cytomegalovirus'', which in turn is a member of the viral family known as ''Herpesviridae'' or herpesviruses. It is also commonly called ...
(CMV), another type of herpes virus. This virus is found in body fluids including saliva
Saliva (commonly referred to as spit) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DNA can be ...
, urine
Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excretion, excreted from the body through the urethra.
Cel ...
, 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 ...
, and tears
Tears are a clear liquid secreted by the lacrimal glands (tear gland) found in the eyes of all land mammals. Tears are made up of water, electrolytes, proteins, lipids, and mucins that form layers on the surface of eyes. The different types of ...
.[Larsen, Laura. ''Sexually Transmitted Diseases Sourcebook. Health Reference Series Detroit'': Omnigraphics, Inc., 2009. Online.] A person becomes infected with this virus
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsky's 1 ...
by direct contact with infected body fluids. Cytomegalovirus is most commonly transmitted through kissing and sexual intercourse. It can also be transferred from an infected mother to her unborn child. This virus is often "silent" because the signs and symptoms cannot be felt by the person infected. However, it can cause life-threatening illness in infants, people with HIV
The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
, transplant recipients, and those with weak immune systems
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinters, ...
. For those with weak immune systems, cytomegalovirus can cause more serious illnesses such as pneumonia
Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severity ...
and inflammations of the retina
The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then ...
, esophagus
The esophagus (American English) or oesophagus (British English; both ), non-technically known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to the ...
, 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 ...
, large intestine
The large intestine, also known as the large bowel, is the last part of the gastrointestinal tract and of the digestive system in tetrapods. Water is absorbed here and the remaining waste material is stored in the rectum as feces before being r ...
, and brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
. Approximately 90% of the human population has been infected with cytomegalovirus by the time they reach adulthood, but most are unaware of the infection. Once a person becomes infected with cytomegalovirus, the virus stays in their body fluids throughout the person's lifetime.
Transmission
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 ...
infection is spread via saliva
Saliva (commonly referred to as spit) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DNA can be ...
, and has an incubation period
Incubation period (also known as the latent period or latency period) is the time elapsed between exposure to a pathogenic organism, a chemical, or radiation, and when symptoms and signs are first apparent. In a typical infectious disease, the i ...
of four to seven weeks. The length of time that an individual remains contagious
Contagious may refer to:
* Contagious disease
Literature
* Contagious (magazine), a marketing publication
* ''Contagious'' (novel), a science fiction thriller novel by Scott Sigler
Music
Albums
*''Contagious'' (Peggy Scott-Adams album), 1997
* ...
is unclear, but the chances of passing the illness to someone else may be the highest during the first six weeks following infection. Some studies indicate that a person can spread the infection for many months, possibly up to a year and a half.
Pathophysiology
The virus replicates first within epithelial cell
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
s in the pharynx
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 struc ...
(which causes pharyngitis
Pharyngitis is inflammation of the back of the throat, known as the pharynx. It typically results in a sore throat and fever. Other symptoms may include a Rhinorrhea, runny nose, cough, headache, difficulty swallowing, swollen lymph nodes, and a ...
, or sore throat), and later primarily within 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 (which are invaded via their CD21
Complement receptor type 2 (CR2), also known as complement C3d receptor, Epstein-Barr virus receptor, and CD21 (cluster of differentiation 21), is a protein that in humans is encoded by the CR2 gene.
CR2 is involved in the complement system. It ...
). The host immune response involves cytotoxic (CD8-positive) T cell
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
s against infected B lymphocytes, resulting in enlarged, atypical lymphocytes ( Downey cells).
When the infection is acute (recent onset, instead of chronic), heterophile
Heterophile antibodies are antibodies induced by external antigens ( heterophile antigens).
Some cross-react with self-antigens. For example, in rheumatic fever, antibodies against group A streptococcal cell walls can also react with (and thu ...
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 ...
are produced.[
]Cytomegalovirus
''Cytomegalovirus'' (''CMV'') (from ''cyto-'' 'cell' via Greek - 'container' + 'big, megalo-' + -''virus'' via Latin 'poison') is a genus of viruses in the order ''Herpesvirales'', in the family ''Herpesviridae'', in the subfamily ''Betaherpe ...
, adenovirus
Adenoviruses (members of the family ''Adenoviridae'') are medium-sized (90–100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from the ...
and ''Toxoplasma gondii
''Toxoplasma gondii'' () is an obligate intracellular parasitic protozoan (specifically an apicomplexan) that causes toxoplasmosis. Found worldwide, ''T. gondii'' is capable of infecting virtually all warm-blooded animals, but felids, such as d ...
'' (toxoplasmosis
Toxoplasmosis is a parasitic disease caused by ''Toxoplasma gondii'', an apicomplexan. Infections with toxoplasmosis are associated with a variety of neuropsychiatric and behavioral conditions. Occasionally, people may have a few weeks or months ...
) infections can cause symptoms similar to infectious mononucleosis, but a heterophile antibody test will test negative and differentiate those infections from infectious mononucleosis.[
Mononucleosis is sometimes accompanied by secondary ]cold agglutinin disease
Cold agglutinin disease (CAD) is a rare disease, rare autoimmune disease characterized by the presence of high concentrations of circulating cold sensitive antibodies, usually IgM and autoantibodies that are also active at temperatures below , dir ...
, an autoimmune disease
An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...
in which abnormal circulating antibodies directed against red blood cell
Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
s can lead to a form of autoimmune hemolytic anemia
Autoimmune hemolytic anemia (AIHA) occurs when antibodies directed against the person's own red blood cells (RBCs) cause them to burst (lyse), leading to an insufficient number of oxygen-carrying red blood cells in the circulation. The lifetime of ...
. The cold agglutinin detected is of anti-i specificity.
Diagnosis
Diagnostic modalities for infectious mononucleosis include:
* Person's age, with highest risk at 10 to 30 years.[
* ]Medical history
The medical history, case history, or anamnesis (from Greek: ἀνά, ''aná'', "open", and μνήσις, ''mnesis'', "memory") of a patient is information gained by a physician by asking specific questions, either to the patient or to other peo ...
, such as close contact with other people with infectious mononucleosis, and the presence and time of onset of "mononucleosis-like symptoms" such as 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 ...
and 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 ...
.
* Physical examination
In a physical examination, medical examination, or clinical examination, a medical practitioner examines a patient for any possible medical signs or symptoms of a medical condition. It generally consists of a series of questions about the patien ...
, including palpation of any enlarged lymph nodes
Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In cl ...
in the neck, or enlarged spleen
Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant (LUQ) of the human abdomen. Splenomegaly is one of the four cardinal signs of ''hypersplenism'' which include: some reduction in number of circulating ...
.
* The heterophile antibody test is a screening
Screening may refer to:
* Screening cultures, a type a medical test that is done to find an infection
* Screening (economics), a strategy of combating adverse selection (includes sorting resumes to select employees)
* Screening (environmental), a ...
test that gives results within a day, but has significantly less than full sensitivity (70–92%) in the first two weeks after clinical symptoms begin.[
* Serological tests take longer time than the heterophile antibody test, but are more accurate.
]
Physical examination
The presence of an enlarged spleen
Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant (LUQ) of the human abdomen. Splenomegaly is one of the four cardinal signs of ''hypersplenism'' which include: some reduction in number of circulating ...
, and swollen posterior cervical
In anatomy, cervical is an adjective that has two meanings:
# of or pertaining to any neck.
# of or pertaining to the female cervix: i.e., the ''neck'' of the uterus.
*Commonly used medical phrases involving the neck are
**cervical collar
**cerv ...
, axillary, and inguinal lymph node
Inguinal lymph nodes are lymph nodes in the human groin. Located in the femoral triangle of the inguinal region, they are grouped into superficial and deep lymph nodes. The superficial have three divisions: the superomedial, superolateral, and inf ...
s are the most useful to suspect a diagnosis of infectious mononucleosis. On the other hand, the absence of swollen cervical lymph nodes 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 an enlarged spleen means it should not be used as evidence against infectious mononucleosis.[ A physical examination may also show ]petechiae
A petechia () is a small red or purple spot (≤4 mm in diameter) that can appear on the skin, conjunctiva, retina, and mucous membranes which is caused by haemorrhage of capillaries. The word is derived from Italian , 'freckle,' of obscure origin ...
in the palate
The palate () is the roof of the mouth in humans and other mammals. It separates the oral cavity from the nasal cavity.
A similar structure is found in crocodilians, but in most other tetrapods, the oral and nasal cavities are not truly sepa ...
.[
]
Heterophile antibody test
The heterophile antibody test, or monospot test, works by agglutination of red blood cells from guinea pigs, sheep and horses. 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).[ About 90% of diagnosed people have heterophile antibodies by week 3, disappearing in under a year. The ]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 ...
involved in the test do not interact with the Epstein–Barr virus or any of its antigen
In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
s.[
The monospot test is not recommended for general use by the ]CDC
The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
due to its poor accuracy.
Serology
Serologic tests detect 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 ...
directed against the Epstein–Barr virus. Immunoglobulin G
Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG a ...
(IgG), when positive, mainly reflects a past infection, whereas immunoglobulin M
Immunoglobulin M (IgM) is one of several isotypes of antibody (also known as immunoglobulin) that are produced by vertebrates. IgM is the largest antibody, and it is the first antibody to appear in the response to initial exposure to an antig ...
(IgM) mainly reflects a current infection. EBV-targeting antibodies can also be classified according to which part of the virus they bind to:
* Viral capsid antigen (VCA):
:*Anti-VCA IgM appear early after infection, and usually, disappear within 4 to 6 weeks.[
:*Anti-VCA IgG appears in the acute phase of EBV infection, reaches a maximum at 2 to 4 weeks after onset of symptoms and thereafter declines slightly and persists for the rest of a person’s life.][
* Early antigen (EA)
:*Anti-EA IgG appears in the acute phase of illness and disappears after 3 to 6 months. It is associated with having an active infection. Yet, 20% of people may have antibodies against EA for years despite having no other sign of infection.][
* EBV nuclear antigen (EBNA)
:*Antibody to EBNA slowly appears 2 to 4 months after the onset of symptoms and persists for the rest of a person’s life.][
When negative, these tests are more accurate than the heterophile antibody test in ruling out infectious mononucleosis. When positive, they feature similar specificity 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.
]
Other tests
* Epstein–Barr nuclear antigen detection. 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
Transaminases or aminotransferases are enzymes that catalyze a transamination reaction between an amino acid and an α-keto acid. They are important in the synthesis of amino acids, which form proteins.
Function and mechanism
An amino acid co ...
levels are highly suggestive of infectious mononucleosis, occurring in up to 50% of people.[
* By ]blood film
A blood smear, peripheral blood smear or blood film is a thin layer of blood smeared on a glass microscope slide and then stained in such a way as to allow the various blood cells to be examined microscopically. Blood smears are examined in the ...
, one diagnostic criterion for infectious mononucleosis is the presence of 50% lymphocyte
A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...
s with at least 10% atypical lymphocytes (large, irregular nuclei), while the person also has fever, pharyngitis, and swollen lymph nodes
Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...
. The atypical lymphocytes resembled monocyte
Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also inf ...
s when they were first discovered, thus the term "mononucleosis" was coined.
* A fibrin ring granuloma may be present.
Differential diagnosis
About 10% of people who present a clinical picture of infectious mononucleosis do not have an acute Epstein–Barr-virus infection. A differential diagnosis of acute infectious mononucleosis needs to take into consideration acute cytomegalovirus infection and ''Toxoplasma gondii
''Toxoplasma gondii'' () is an obligate intracellular parasitic protozoan (specifically an apicomplexan) that causes toxoplasmosis. Found worldwide, ''T. gondii'' is capable of infecting virtually all warm-blooded animals, but felids, such as d ...
'' infections. Because their management is much the same, it is not always helpful, or possible, to distinguish between Epstein–Barr-virus mononucleosis and cytomegalovirus infection. However, in pregnant women, differentiation of mononucleosis from toxoplasmosis
Toxoplasmosis is a parasitic disease caused by ''Toxoplasma gondii'', an apicomplexan. Infections with toxoplasmosis are associated with a variety of neuropsychiatric and behavioral conditions. Occasionally, people may have a few weeks or months ...
is important, since it is associated with significant consequences for the fetus
A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal deve ...
.
Acute HIV infection
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 ma ...
can mimic signs similar to those of infectious mononucleosis, and tests should be performed for pregnant women for the same reason as toxoplasmosis.[
People with infectious mononucleosis are sometimes misdiagnosed with a streptococcal pharyngitis (because of the symptoms of fever, ]pharyngitis
Pharyngitis is inflammation of the back of the throat, known as the pharynx. It typically results in a sore throat and fever. Other symptoms may include a Rhinorrhea, runny nose, cough, headache, difficulty swallowing, swollen lymph nodes, and a ...
and adenopathy
Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammation, inflammatory type (the most common type) is lymphadenitis, producing swelling (medical), swolle ...
) and are given antibiotics such as ampicillin
Ampicillin is an antibiotic used to prevent and treat a number of bacterial infections, such as respiratory tract infections, urinary tract infections, meningitis, salmonellosis, and endocarditis. It may also be used to prevent group B strepto ...
or amoxicillin
Amoxicillin is an antibiotic medication used to treat a number of bacterial infections. These include middle ear infection, strep throat, pneumonia, skin infections, and urinary tract infections among others. It is taken by mouth, or less c ...
as treatment.
Other conditions from which to distinguish infectious mononucleosis include leukemia
Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...
, tonsillitis
Tonsillitis is inflammation of the tonsils in the upper part of the throat. It can be acute or chronic. Acute tonsillitis typically has a rapid onset. Symptoms may include sore throat, fever, enlargement of the tonsils, trouble swallowing, and en ...
, diphtheria
Diphtheria is an infection caused by the bacterium '' Corynebacterium diphtheriae''. Most infections are asymptomatic or have a mild clinical course, but in some outbreaks more than 10% of those diagnosed with the disease may die. Signs and s ...
, common cold
The common cold or the cold is a viral infectious disease of the upper respiratory tract that primarily affects the respiratory mucosa of the nose, throat, sinuses, and larynx. Signs and symptoms may appear fewer than two days after exposu ...
and influenza
Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptoms ...
(flu).[
]
Treatment
Infectious mononucleosis is generally self-limiting (biology), self-limiting, so only symptomatic or supportive treatments are used. The need for rest and return to usual activities after the acute phase of the infection may reasonably be based on the person's general energy levels.[ Nevertheless, in an effort to decrease the risk of ]splenic rupture
A splenic injury, which includes a ruptured spleen, is any injury to the spleen. The rupture of a normal spleen can be caused by trauma, such as a traffic collision.
Signs and symptoms
In minor injuries with little bleeding, there may be abdomin ...
experts advise avoidance of contact sports and other heavy physical activity, especially when involving increased abdominal pressure or the Valsalva maneuver (as in rowing (sport), rowing or weight training), for at least the first 3–4 weeks of illness or until enlargement of the spleen has resolved, as determined by a treating physician.
Medications
Paracetamol (acetaminophen) and non-steroidal anti-inflammatory drug, NSAIDs, such as ibuprofen
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used for treating pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus arte ...
, may be used to reduce fever and pain. Prednisone, a corticosteroid, while used to try to reduce throat pain or enlarged tonsils, remains controversial due to the lack of evidence that it is effective and the potential for side effects. Intravenous corticosteroids, usually hydrocortisone or dexamethasone, are not recommended for routine use but may be useful if there is a risk of airway obstruction, a thrombocytopenia, very low platelet count, or hemolytic anemia.[Antibiotic Expert Group. Therapeutic guidelines: Antibiotic. 13th ed. North Melbourne: Therapeutic Guidelines; 2006.]
Antiviral agents act by inhibiting viral DNA replication. There is little evidence to support the use of antivirals such as aciclovir and valacyclovir although they may reduce initial viral shedding. Antivirals are expensive, risk causing resistance to antiviral agents, and (in 1% to 10% of cases) can cause unpleasant side effects. Although antivirals are not recommended for people with simple infectious mononucleosis, they may be useful (in conjunction with steroids) in the management of severe EBV manifestations, such as EBV meningitis, peripheral neuritis, hepatitis, or hematologic complications.
Although antibiotics exert no antiviral action they may be indicated to treat bacterial secondary infections of the throat, such as with streptococcus (strep throat
Streptococcal pharyngitis, also known as streptococcal sore throat (strep throat), is pharyngitis (an infection of the pharynx, the back of the throat) caused by ''Streptococcus pyogenes'' a gram-positive, group A streptococcus. Common symptom ...
). However, ampicillin
Ampicillin is an antibiotic used to prevent and treat a number of bacterial infections, such as respiratory tract infections, urinary tract infections, meningitis, salmonellosis, and endocarditis. It may also be used to prevent group B strepto ...
and amoxicillin
Amoxicillin is an antibiotic medication used to treat a number of bacterial infections. These include middle ear infection, strep throat, pneumonia, skin infections, and urinary tract infections among others. It is taken by mouth, or less c ...
are not recommended during acute 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 ...
infection as a diffuse rash may develop.
Observation
Splenomegaly is a common symptom of infectious mononucleosis and health care providers may consider using abdominal ultrasonography to get insight into the enlargement of a person's spleen.[, which cites
*
* ] However, because spleen size varies greatly, ultrasonography is not a valid technique for assessing spleen enlargement and should not be used in typical circumstances or to make routine decisions about fitness for playing sports.
Prognosis
Serious complication (medicine), complications are uncommon, occurring in less than 5% of cases:
* Central nervous system, CNS complications include meningitis, encephalitis, hemiplegia, Guillain–Barré syndrome, and transverse myelitis. Prior infectious mononucleosis has been linked to the development of multiple sclerosis.
* Hematology, Hematologic: Autoimmune hemolytic anemia, Hemolytic anemia (direct Coombs test is positive) and various cytopenias, and bleeding (caused by thrombocytopenia) can occur.
* Mild jaundice
Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...
* Hepatitis with the Epstein–Barr virus is rare.
* Upper airway obstruction from Palatine tonsil#Tonsillar hypertrophy, tonsillar hypertrophy is rare.
* Fulminant disease course of immunodeficiency, immunocompromised people are rare.
* Splenic rupture is rare.
* Myocarditis and pericarditis are rare.
* Postural orthostatic tachycardia syndrome
* Chronic fatigue syndrome
* Cancers associated with the Epstein-Barr virus include Burkitt's lymphoma, Hodgkin's lymphoma and lymphomas in general as well as Nasopharyngeal carcinoma, nasopharyngeal and gastric carcinoma.
* Hemophagocytic lymphohistiocytosis
Once the acute symptoms of an initial infection disappear, they often do not return. But once infected, the person carries the virus for the rest of their life. The virus typically lives dormant in B lymphocytes. Independent infections of mononucleosis may be contracted multiple times, regardless of whether the person is already carrying the virus dormant. Periodically, the virus can reactivate, during which time the person is again infectious, but usually without any symptoms of illness.[ Usually, a person with IM 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.][
]
History
The characteristic symptomatology of infectious mononucleosis does not appear to have been reported until the late nineteenth century. In 1885, the renowned Russian pediatrician Nil Filatov reported an infectious process he called "idiopathic adenitis" exhibiting symptoms that correspond to infectious mononucleosis, and in 1889 a German balneologist and pediatrician, Emil Pfeiffer, independently reported similar cases (some of lesser severity) that tended to cluster in families, for which he coined the term ''Drüsenfieber'' ("glandular fever").[
The word ''mononucleosis'' has several word sense, senses,] but today it usually is used in the sense of infectious mononucleosis, which is caused by EBV.
The term "infectious mononucleosis" was coined in 1920 by Thomas Peck Sprunt and Frank Alexander Evans in a classic clinical description of the disease published in the ''Bulletin of the Johns Hopkins Hospital'', entitled "Mononuclear leukocytosis in reaction to acute infection (infectious mononucleosis)". A lab test for infectious mononucleosis was developed in 1931 by Yale School of Public Health Professor John Rodman Paul and Walls Willard Bunnell based on their discovery of heterophile antibodies in the sera of persons with the disease. The Paul-Bunnell Test or PBT was later replaced by the heterophile antibody test.
The Epstein–Barr virus was first identified in Burkitt's lymphoma cells by Anthony Epstein, Michael Anthony Epstein and Yvonne Barr at the University of Bristol in 1964. The link with infectious mononucleosis was uncovered in 1967 by Werner and Gertrude Henle at the Children's Hospital of Philadelphia, after a laboratory technician handling the virus contracted the disease: comparison of serum samples collected from the technician before and after the onset revealed development of 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 ...
to the virus.
Yale School of Public Health epidemiologist Alfred E. Evans confirmed through testing that mononucleosis was transmitted mainly through kissing leading to it being referred to colloquially as "the kissing disease".
References
External links
*
{{DEFAULTSORT:Infectious Mononucleosis
Epstein–Barr virus–associated diseases
Virus-related cutaneous conditions
Cytomegalovirus-associated diseases
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