Infectious mononucleosis

pharyngitis in a person with infectious mononucleosis (mild pharyngitis, with or without tonsillitis). • Fever – usually lasting 14 days; often mild. • Swollen glands –  mobile; usually located around the back of the neck (posterior cervical lymph nodes) and sometimes throughout the body. Another major symptom is feeling tired. Mild fever, swollen neck glands and body aches may also persist beyond 4 weeks. Palatal enanthem can also occur, but is relatively uncommon. Occasional cases of erythema nodosum and erythema multiforme have been reported. Complications Spleen enlargement is common in the second and third weeks, although this may not be apparent on physical examination. Rarely, the spleen may rupture. There may also be some enlargement of the liver. It generally gets better on its own in people who are otherwise healthy. Older adults Infectious mononucleosis mainly affects younger adults. 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, a member of the Herpesviridae family of DNA viruses. It is one of the most commonly found viruses 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, 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 develop infectious mononucleosis. Cytomegalovirus About 5–7% of cases of infectious mononucleosis are caused by human cytomegalovirus (CMV), another type of herpes virus. This virus is found in body fluids including saliva, urine, blood, tears, breast milk and genital secretions. Once a person becomes infected with cytomegalovirus, the virus stays in their body throughout the person's lifetime. During this latent phase, the virus can be detected only in monocytes. Other causes Toxoplasma gondii, a parasitic protozoon, is responsible for less than 1% of the infectious mononucleosis cases. Viral hepatitis, adenovirus, rubella, and herpes simplex viruses have also been reported as rare causes of infectious mononucleosis. Transmission Epstein–Barr virus infection is spread via saliva, and has an incubation period of four to seven weeks. The length of time that an individual remains contagious is unclear. The chances of passing the illness to someone else may be 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 cells in the pharynx (which causes pharyngitis, or sore throat), and later primarily within B cells (which are invaded via their CD21). The host immune response involves cytotoxic (CD8-positive) T cells against infected B lymphocytes, resulting in enlarged, reactive lymphocytes (Downey cells). When the infection is acute (recent onset, instead of chronic), heterophile antibodies are produced. Mononucleosis is sometimes accompanied by secondary cold agglutinin disease, an autoimmune disease in which abnormal circulating antibodies directed against red blood cells can lead to a form of autoimmune hemolytic anemia. The cold agglutinin detected is of anti-i specificity. ==Diagnosis==

The disease is diagnosed based on: Physical examination The presence of an enlarged spleen, and swollen posterior cervical, axillary, and inguinal lymph nodes are the most useful to suspect a diagnosis of infectious mononucleosis. On the other hand, the absence of swollen cervical lymph nodes and fatigue is 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. Other tests • Elevated hepatic transaminase levels are highly suggestive of infectious mononucleosis, occurring in up to 50% of people. while the person also has fever, pharyngitis, and swollen lymph nodes. The reactive lymphocytes resembled monocytes when they were first discovered, thus the term "mononucleosis" was coined. • A fibrin ring granuloma may be present in the liver or bone marrow. 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 infections. Because their management is similar, 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 is important, since it is associated with significant consequences for the fetus. Other conditions from which to distinguish infectious mononucleosis include leukemia, tonsillitis, diphtheria, common cold and influenza (flu). ==Treatment==

Infectious mononucleosis is generally 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. Medications Paracetamol (acetaminophen) and NSAIDs, such as ibuprofen, 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. Aspirin should not be given to under-16s due to the risk of Reye syndrome. 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 very low platelet count, or hemolytic anemia. Antiviral agents act by inhibiting viral DNA replication. Antivirals are expensive, risk causing resistance to antiviral agents, and (in 1% to 10% of cases) can cause unpleasant side effects. Although antibiotics exert no antiviral action they may be indicated to treat bacterial secondary infections of the throat, such as with streptococcus (strep throat). However, ampicillin and amoxicillin are not recommended during acute Epstein–Barr virus infection as a diffuse rash may develop. Observation Splenomegaly is a common symptom of infectious mononucleosis, and healthcare providers may consider using abdominal ultrasonography to get insight into the enlargement of a person's spleen. However, because spleen size varies greatly, ultrasonography is not a valid technique for assessing spleen enlargement. It should not be used in typical circumstances or to make routine decisions about fitness for playing sports. ==Prognosis==

Serious complications are uncommon, occurring in less than 5% of cases: • CNS complications include meningitis, encephalitis, hemiplegia, Guillain–Barré syndrome, and transverse myelitis. Prior infectious mononucleosis has been linked to the development of multiple sclerosis. • Hematologic: Hemolytic anemia (direct Coombs test is positive) and various cytopenias, and bleeding (caused by thrombocytopenia) can occur. • Hemophagocytic lymphohistiocytosis Once the acute symptoms of an initial infection resolve, 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. ==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 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. Before the identification of infectious mononucleosis as a distinct disease, it was most often called "glandular fever", and there were few tests to determine an infection. Notable confirmed outbreaks of mononucleosis in the late 19th and early 20th centuries include a large outbreak in an Ohio community in 1896, an outbreak in which 87 people were infected in a community in the Falkland Islands, and an outbreak at the U.S. Naval Base in Coronado, California, where 220 individuals were infected by the virus. The Epstein–Barr virus was first identified in Burkitt's lymphoma cells by 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 to the virus. Yale School of Public Health epidemiologist Alfred S. Evans confirmed through testing that mononucleosis was transmitted mainly through kissing, leading to it being referred to colloquially as "the kissing disease". ==References==