Infectious mononucleosis

Infectious mononucleosis is caused by the Epstein-Barr virus (EBV, human herpesvirus type 4) and is characterized by increased fatigue, fever, pharyngitis, and lymphadenopathy.

Fatigue may persist for weeks or months. Serious complications include splenic rupture, neurological syndromes, but are rare. The diagnosis of infectious mononucleosis is clinical or by testing for heterophilic antibodies. Treatment of infectious mononucleosis is symptomatic.

An anthroponotic infectious disease caused by the Epstein-Barr virus with an aerosol transmission mechanism. Characterized by a cyclic course, fever, acute tonsillitis, pharyngitis, severe damage to lymphoid tissue, hepatosplenomegaly, lymphomonocytosis, and the appearance of atypical mononuclear cells in the blood.

ICD-10 code

B27.0. Mononucleosis caused by gammaherpes virus.

What causes infectious mononucleosis?

Infectious mononucleosis is caused by the Epstein-Barr virus, which infects 50% of children under 5 years of age, its host is a human. After initial replication in the nasopharynx, the virus affects B-lymphocytes responsible for the synthesis of immunoglobulins, including heterophilic antibodies. Morphologically, atypical lymphocytes are detected, mainly T-cells with the CD8+ phenotype.

After primary infection, Epstein-Barr virus remains in the body throughout life, mainly in B cells with asymptomatic persistence in the oropharynx. It is detected in the oropharyngeal secretions of 15-25% of healthy EBV-seropositive adults. Prevalence and titer are higher in immunocompromised individuals (e.g., organ transplant recipients, HIV-infected patients).

The Epstein-Barr virus is not transmitted from the environment and is not very contagious. Transmission can occur through blood transfusions, but most often infection occurs through kissing infected individuals who are asymptomatic. Only 5% of patients become infected through contact with patients with acute infection. Infection of young children occurs more often in groups with a low socioeconomic level and in groups.

Epstein-Barr infection is statistically associated with and possibly causes Burkitt lymphoma, which develops from B cells in immunocompromised patients, also with a risk of developing nasopharyngeal carcinoma. The virus does not cause chronic fatigue syndrome. However, it can cause unexplained fever, interstitial pneumonitis, pancytopenia, and uveitis (eg, chronic active EBV).

What are the symptoms of infectious mononucleosis?

Most young people with primary Epstein-Barr infection are asymptomatic. Symptoms of infectious mononucleosis are more common in older children and adults.

The incubation period of infectious mononucleosis is 30-50 days. Weakness usually develops first, lasting several days, a week or more, then fever, pharyngitis, and lymphadenopathy. Not all of these symptoms necessarily occur. Weakness and fatigue may last for months, but are most pronounced in the first 2-3 weeks. Fever peaks at lunchtime or early evening, with a maximum rise in temperature to 39.5 "C, sometimes reaching 40.5 "C. When weakness and fever predominate in the clinical picture (the so-called typhoid form), exacerbation and resolution are slower. Pharyngitis may be severe, accompanied by pain, exudation, and be complicated by streptococcal infection. Adenopathy of the anterior and posterior cervical lymph nodes is characteristic; adenopathy is symmetrical. Sometimes enlargement of the lymph nodes is the only manifestation of the disease.

Approximately 50% of cases show splenomegaly with maximal enlargement of the spleen during the 2nd and 3rd weeks of illness, with its edge usually palpable. Moderate enlargement of the liver and its tenderness to percussion or palpation are detected. Less frequently, maculopapular rash, jaundice, periorbital edema, and enanthem of the hard palate are detected.

Complications of infectious mononucleosis

Although patients usually recover, complications of infectious mononucleosis can be dramatic.

Among the neurological complications of infectious mononucleosis, one should remember about encephalitis, seizures, Guillain-Barré syndrome, peripheral neuropathy, aseptic meningitis, myelitis, cranial nerve palsy and psychosis. Encephalitis can manifest itself with cerebellar disorders or have a more serious and progressive course, similar to herpes encephalitis, but with a tendency to self-resolution.

Hematologic abnormalities are usually self-limiting. Granulocytopenia, thrombocytopenia, and hemolytic anemia may occur. Transient, moderate granulocytopenia or thrombocytopenia occurs in approximately 50% of patients; bacterial infection or bleeding are less common. Hemolytic anemia results from the development of anti-specific autoantibodies.

A spleen rupture can be one of the most serious consequences of infectious mononucleosis. It occurs as a result of a significant increase in its size and swelling of the capsule (maximum - on the 10th-21st day of the disease), and trauma occurs in approximately half of patients. A spleen rupture is accompanied by pain, but sometimes manifests itself as painless hypotension.

Rare respiratory complications of infectious mononucleosis include upper airway obstruction due to laryngeal and peritracheal lymph node adenopathy; these complications respond to corticosteroid therapy. Clinically asymptomatic interstitial pulmonary infiltrates are common in children and are readily detectable on radiographic examination.

Liver complications occur in about 95% of patients and include increased aminotransferases (2-3 times higher than normal and returning to baseline after 3-4 weeks). If jaundice and a more significant increase in liver enzyme activity develop, other causes of liver damage should be excluded.

Generalized EBV infection occasionally occurs but tends to run in families, especially with X-linked lymphoproliferative syndrome. These individuals who have had EBV infection have an increased risk of developing agammaglobulinemia or lymphoma.

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How is infectious mononucleosis diagnosed?

Infectious mononucleosis should be suspected in patients with typical clinical symptoms. Exudative pharyngitis, lymphadenopathy of the anterior cervical lymph nodes and fever require differential diagnosis with the disease caused by beta-hemolytic streptococci; infectious mononucleosis is supported by involvement of the posterior cervical lymph nodes or generalized lymphadenopathy and hepatosplenomegaly. Moreover, detection of streptococci in the oropharynx does not exclude infectious mononucleosis. Cytomegalovirus infection may manifest itself with similar symptoms - atypical lymphocytosis, hepatosplenomegaly, hepatitis, but in the absence of pharyngitis. Infectious mononucleosis should be differentiated from toxoplasmosis, hepatitis B, rubella, primary HIV infection, adverse reactions to drugs (appearance of atypical lymphocytes).

Laboratory methods include peripheral blood leukocyte counting and heterophile antibody testing. Atypical lymphocytes account for more than 80% of the total leukocyte count. Individual lymphocytes may resemble those in leukemia, but overall they are very heterogeneous (unlike leukemia).

Heterophile antibodies are assessed using the agglutination test. Antibodies are detected in only 50% of patients younger than 5 years, but in 90% of recovering patients and adults who have had primary EBV infection. The titer and frequency of heterophile antibodies increase between the 2nd and 3rd weeks of illness. Thus, if the probability of the disease is high and heterophile antibodies are not detected, it is advisable to repeat this test 7-10 days after the onset of the first symptoms. If the test remains negative, it is advisable to evaluate the level of antibodies to EBV. If their level does not correspond to acute EBV infection, CMV infection should be considered. Heterophile antibodies can persist for 6-12 months.

In children under 4 years of age, when heterophile antibodies may not be detected in principle, acute EBV infection is indicated by the presence of IgM antibodies to the capsid antigen of the virus; these antibodies disappear 3 months after the infection, but, unfortunately, these tests are only performed in certain laboratories.

How is infectious mononucleosis treated?

Infectious mononucleosis is usually self-limiting. The duration of the disease varies; the acute phase lasts about 2 weeks. In general, 20% of patients can return to work or school within 1 week, 50% within 2 weeks. Fatigue can last for several weeks, less often - 1-2% of cases - for months. Mortality is less than 1% and is associated with the development of complications (e.g. encephalitis, ruptured spleen, airway obstruction).

Treatment of infectious mononucleosis is symptomatic. In the acute phase of the disease, patients should be provided with rest, but as weakness, fever, and pharyngitis disappear, they can quickly return to normal activity. To prevent rupture of the spleen, patients should avoid lifting weights and playing sports for 1 month after the disease and until the spleen has returned to normal size (under ultrasound control).

Although glucocorticoids can reduce body temperature and alleviate pharyngitis symptoms fairly quickly, they are not recommended for uncomplicated cases. Glucocorticoids are useful in the development of complications such as airway obstruction, hemolytic anemia, and thrombocytopenia. Oral or intravenous acyclovir can reduce EBV shedding from the oropharynx, but there is no convincing evidence to support the clinical use of these drugs.

What is the prognosis for infectious mononucleosis?

Infectious mononucleosis has a favorable prognosis. Fatal outcomes are casuistically rare (rupture of the spleen, airway obstruction, encephalitis).