Infectious mononucleosis

Infectious mononucleosis

Infectious mononucleosis is a common infection that results in fever, sore throat, and cervical lymphadenopathy accompanied by lymphocytosis. The cause of infectious mononucleosis is the Epstein-Barr virus (known as EBV or human herpesvirus 4).

Manifestations

Infectious mononucleosis has a prodromal period in which they occur headache, fatigue, and tiredness during the first 4-5 falls. After the prodromal period, a triad of symptoms usually occurs – fever, pharyngitis, and lymphadenopathy. Most younger children with infectious mononucleosis are asymptomatic; symptoms are more pronounced in previously uninfected younger adults.
Major complications occur in 1-5% of cases of infectious mononucleosis. The most common complications are lymphocytic meningitis,  encephalitis, encephalomyelitis, polyneuritis, mononeuritis, and  Guillain-Barre syndrome. Guillain-Barre syndrome is a condition that can lead to respiratory paralysis and death. Rupture of the spleen can also occur but is extremely rare. Severe tonsillitis can lead to airway obstruction if no tracheotomy is performed.

Signs and symptoms of infectious mononucleosis

  • fever: in adults 38.3-28.9 ° C; children don’t have to have a fever,
  • cervical lymphadenopathy,
  • pharyngitis with diffuse pharyngeal inflammation and swelling of the tonsils; maybe exudative or non-exudative,
  • bilateral edema of the upper eyelids (palpebral edema),
  • early in the disease, the appearance of the non-purulent maculopapular rash,
  • petechiae on the hands and soft palate may appear later in the disease (in 30% of symptomatic patients),
  • swelling of the anterior and posterior cervical lymph nodes, plus axillary, epitrochlear, mediastinal, and mesenteric nodes,
  • splenomegaly (occurs in about 50% of cases of acute mononucleosis and is a late invention),
  • hepatomegaly (occurs in about 10% of patients),
  • jaundice (occurs in about 5% of cases),
  • early in the disease, cutaneous allergies, and reduced immune response to mitogens and antigens.

Epidemiology

  • EBV infection occurs worldwide and usually a subclinical infection in younger children.
  • Infectious mononucleosis is most commonly seen in young adults aged 15-25.
  • The incubation period lasts 1-2 months. Many patients cannot even remember where they may have been exposed to EBV.
  • About 70% of patients become infected with EBV by 30. years of age.
  • Since the EBV virus is minimally contagious, a person must theoretically be exposed to an infected person several times before becoming infected with the virus.
  • After recovery, the virus remains in saliva for months. More than 90% of people infected with EBV intermittently have the virus present throughout their lives, even in asymptomatic stages.
  • EBV is acquired by contact with infected cervical and oral secretions. Transmission can also be through blood transfusions.

Pathogenesis

Oropharyngeal epithelial cells are the portal of EBV infections. The virus is transmitted primarily by repeated contact with oropharyngeal secretions and is primarily transmitted through adults 30-50 days after infection or children 10-14 days after infection. EBV can be isolated from saliva, blood, and lymph. EBV invades B lymphocytes via their CD21 receptors; within 18-24 hours, EBV antigens can be detected in lymphocyte nuclei.
The signs and symptoms of infectious mononucleosis result from virus replication and the host’s immune response to viral antigens. Infected B lymphocytes spread infection by the reticuloendothelial system (e.g., liver, spleen, and peripheral lymph nodes). EBV B lymphocyte infections result in the humoral and cellular responses to the virus. They initiate B lymphocytes’ proliferation (plasma cells) and immortalization (memory B lymphocytes) without T-helper cells’ role. EBV is a B-cell mitogen that can stimulate many B lymphocytes to become antibody-producing plasma cells.
Many of these antibody-producing plasma cells do not react with EBV antigens. Some of the plasma cells produce antibodies that react with other mammals’ red blood cells, such as sheep. This humoral immune response, called the heterophilic response, is the basis of the serological tests used for infectious mononucleosis (e.g., the heterophile antibody test – the Monospot test). Other plasma cells produce antibodies that react with EBV antigens and can be used to confirm the diagnosis of infectious mononucleosis. As with many other viral infections, the T-lymphocyte response is essential for controlling EBV infection; NK cells and predominantly CD8 cytotoxic T lymphocytes control the proliferation of EBV virus-infected B lymphocytes.
During the acute phase of infectious mononucleosis, nearly 20% of circulating B lymphocytes will produce EBV antigens, while only 1% will produce antigens during convalescence. The virus cannot usually be found free in the blood, but it is present as an immune complex that can cause arthralgias and urticarial rashes during the disease’s acute phase.
Whole virion-producing B lymphocytes are killed by virus-directed cytolysis, while infected non-whole virion-producing B lymphocytes are killed by cytotoxic T lymphocytes that control their proliferation. Lymphocytosis associated with infectious mononucleosis is caused by an increase in circulating activated T and B lymphocytes (also known as Downey cells due to their atypical presence in the peripheral blood). EBV can be detected in oropharyngeal lavage 12-18 months after the disappearance of circulating Downey cells and when the patient has already recovered from the disease. EBV infection lasts a lifetime.

Diagnosis

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Atypical lymphocytes in the peripheral blood, ie. Downey cells are marked in the figure below with a black arrow, and in the upper left corner, a normal lymphocyte is marked with a blue arrow for the possibility of comparison.
Diagnosis of infectious mononucleosis involves identifying atypical lymphocytes in peripheral blood smears. During acute EBV disease, the number of lymphocytes increases to 50-60% of the total number of leukocytes in the peripheral blood (number of 20,000-50,000 / µL), of which 10% are atypical lymphocytes (95% are T lymphocytes, 5% B lymphocytes), or Downey cells. Atypical lymphocytes’ presence is probably the earliest indication of EBV infection but is not specific for mononucleosis. Atypical lymphocytes can also be seen in patients with lymphoproliferative diseases (e.g., Chediak-Higashi syndrome, Wiskott-Aldrich syndrome, X-linked lymphoproliferative diseases), hepatitis, CMV infection, rubella, and roseola. Mild leukocytosis is present, and an increased erythrocyte sedimentation rate is often reported.
As mentioned above, EBV is a B-lymphocyte mitogen that causes many different types of B-lymphocytes to produce antibodies (immunoglobulins). Some plasma cells are induced to multiply and produce immunoglobulins, most commonly immunoglobulin M (IgM), which does not react with EBV-specific antigens but recognizes antigenic domains erythrocytes of sheep, horses, and the like. IgM antibodies, in this case, are called heterophilic antibodies because they react with something other than EBV viral proteins. EBV heterophile antibody titers are highest during the first four weeks of illness, and heterophile antibody titers are often used to detect antibodies that react with sheep or horse erythrocytes rather than EBV proteins. A false negative reaction occurs in about 10% of adults and 50% of children. About 60-90% of adults are positive for heterophile antibodies when tested within the first two weeks of illness. Most children under the age of two are negative for heterophilic antibodies. If heterophilic antibodies cannot be detected, a diagnosis of infectious mononucleosis can be obtained by testing serum for EBV-specific antibodies.

Therapy and prevention

Most cases of infectious mononucleosis are mild or moderate. Therefore, therapy often consists only of rest and analgesics as the primary form of therapy for acute infectious mononucleosis. The symptoms of infectious mononucleosis are very similar to bacterial pharyngitis (caused by Streptococcus pyogenes). If the doctor diagnoses only clinical signs and symptoms, often infectious mononucleosis can be diagnosed as bacterial pharyngitis and treated with antibiotics. Patients with infectious mononucleosis prescribed ampicillin or amoxicillin may develop a rash. The best way to prevent most infectious mononucleosis complications is to expose the virus early in life since children’s symptoms are milder than the disease in adults.

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