Clinical characteristics of infectious mononucleosis. Infectious mononucleosis (Epstein-Barr viral infection)

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Ministry of Education and Science of the Russian Federation

Federal State Autonomous Educational Institution of Higher Professional Education "North-Eastern Federal

University named after M.K.Ammosova"

Medical Institute

Department of Propaedeutics of Childhood Diseases

ABSTRACT ON THE TOPIC:

"TREATMENT OF INFECTIOUS MONONUCLEOSIS".

Completed by: 5th year student of group 502/1

specialty "General Medicine"

Anisimova Alina Ivanovna

Checked by: assistant Marinova L.G.

Yakutsk 2015

Introduction

1. Infectious mononucleosis

5. Treatment

Conclusion

References

Introduction

One of the pressing problems of modern medicine is the high infection rate of the population with one of the representatives of opportunistic pathogens - the Epstein-Barr virus (EBV). Practicing doctors in their daily practice more often encounter clinically manifest forms of primary Epstein-Barr virus infection (EBVI) in the form of acute, usually unverified respiratory infection(more than 40% of cases) or infectious mononucleosis (about 18% of all diseases). In most cases, these diseases are benign and end in recovery, but with lifelong persistence of EBV in the body of the person who has recovered from the disease.

However, in 10-25% of cases, primary EBV infection, which is asymptomatic, and acute EBV infection can have adverse consequences with the formation of lymphoproliferative and oncological diseases, chronic fatigue syndrome, EBV-associated hemophagocytic syndromes, etc.

To date, there are no clear criteria to predict the outcome of primary EBV infection. A doctor who is approached by a patient with acute EBVI always faces the question: what to do in each specific case in order to minimize the risk of developing chronic EBVI and EBV-associated pathological conditions. This is not an idle question, and it is really very difficult to answer, because ?To. There is still no clear pathogenetically substantiated treatment regimen for patients, and existing recommendations often contradict each other.

Epstein virus infectious mononucleosis

1. Infectious mononucleosis

Infectious mononucleosis (mononucleosis infectiosa, Filatov's disease, monocytic tonsillitis, benign lymphoblastosis) is an acute anthroponotic viral infectious disease with fever, damage to the oropharynx, lymph nodes, liver and spleen and specific changes in the hemogram.

Historical data. Clinical manifestations of the disease were first described by N.F. Filatov (“Filatov’s disease”, 1885) and E. Preiffer (1889). Changes in the hemogram have been studied by many researchers (Bernet J., 1909; Tidy G. et al., 1923; Schwartz E., 1929, etc.). In accordance with these characteristic changes, American scientists T. Sprunt and F. Evans called the disease infectious mononucleosis. The pathogen was first isolated by the English pathologist M.A. Epstein and Canadian virologist I. Barr from Burkitt's lymphoma cells (1964). The virus was later named Epstein-Barr virus.

Etiology.

The causative agent of infectious mononucleosis is a DNA genomic virus of the genus Lymphocryptovirus of the Gammaherpesvirinae subfamily of the Herpesviridae family. The virus is able to replicate, including in B lymphocytes; unlike other herpes viruses, it does not cause cell death, but, on the contrary, activates their proliferation. Virions include specific antigens: capsid (VCA), nuclear (EBNA), early (EA) and membrane (MA) antigens. Each of them is formed in a certain sequence and induces the synthesis of corresponding antibodies. In the blood of patients with infectious mononucleosis, antibodies to the capsid antigen first appear, and later antibodies to EA and MA are produced. The pathogen is not stable in the external environment and quickly dies when it dries out, under the influence of high temperature and disinfectants.

Infectious mononucleosis is only one form of infection with the Epstein-Barr virus, which also causes Burkitt's lymphoma and nasopharyngeal carcinoma. Its role in the pathogenesis of a number of other pathological conditions has not been sufficiently studied.

Epidemiology .

The reservoir and source of infection is a person with a manifest or erased form of the disease, as well as a carrier of the pathogen. Infected individuals shed the virus from the last days of incubation and for 6-18 months after the initial infection. The virus is also detected in oropharyngeal washings from 15-25% of seropositive healthy people. The epidemic process is supported by people who have previously had an infection and secrete the pathogen in their saliva for a long time.

Mechanism transfers- aerosol, transmission route - airborne droplets. Very often, the virus is released in saliva, so infection is possible through contact (kissing, sexual intercourse, through hands, toys and household items). Infection can be transmitted through blood transfusions, as well as during childbirth.

Natural susceptibility people are high, however, mild and erased forms of the disease predominate. The presence of innate passive immunity can be evidenced by the extremely low morbidity rate in children in the first year of life. Immunodeficiency states contribute to the generalization of infection.

Basic epidemiological signs. The disease is widespread; Mostly sporadic cases are recorded, sometimes small outbreaks. The polymorphism of the clinical picture and the rather frequent difficulties in diagnosing the disease give reason to believe that the level of officially registered morbidity in Ukraine does not reflect the true extent of the spread of the infection. Teenagers most often get sick; in girls, the maximum incidence is recorded at 14-16 years old, in boys - at 16-18 years old. Therefore, infectious mononucleosis is sometimes also called “students’ disease.” People over 40 years of age rarely get sick, but in HIV-infected people, reactivation of a latent infection is possible at any age. When infected in early childhood primary infection occurs in the form of a respiratory disease, at older ages it is asymptomatic. By the age of 30-35, most people have antibodies to the infectious mononucleosis virus in their blood, so clinically pronounced forms are rarely found among adults. Diseases are recorded throughout the year, somewhat less frequently in the summer months. Infection is facilitated by overcrowding, sharing of shared linen, utensils, and close household contacts.

Immunity after infectious mononucleosis is persistent, recurrent diseases are not observed.

Mortality low. There is information about isolated cases of death due to splenic rupture, laryngeal stenosis and damage to the central nervous system.

Pathogenesis

Penetration of the virus into the upper respiratory tract leads to damage to the epithelium and lymphoid tissue of the oropharynx and nasopharynx. Swelling of the mucous membrane, enlargement of the tonsils and regional lymph nodes are noted. With subsequent viremia, the pathogen invades B lymphocytes; being in their cytoplasm, it disseminates throughout the body. The spread of the virus leads to systemic hyperplasia of lymphoid and reticular tissues, and therefore atypical mononuclear cells appear in the peripheral blood. Lymphadenopathy, swelling of the mucous membrane of the nasal concha and oropharynx develop, the liver and spleen enlarge. Histologically, hyperplasia of lymphoreticular tissue is revealed in all organs, lymphocytic periportal infiltration of the liver with minor degenerative changes in hepatocytes.

Virus replication in B lymphocytes stimulates their active proliferation and differentiation into plasmacytes. The latter secrete immunoglobulins of low specificity. At the same time, during the acute period of the disease, the number and activity of T-lymphocytes increase. Suppressor T cells inhibit the proliferation and differentiation of B lymphocytes. Cytotoxic T lymphocytes destroy virus-infected cells by recognizing membrane virus-induced antigens. However, the virus remains in the body and persists in it throughout subsequent life, causing a chronic course of the disease with reactivation of the infection when immunity decreases.

Expressiveness immunological reactions in infectious mononucleosis allows us to consider it a disease of the immune system, therefore it is classified as a group of diseases of the AIDS-associated complex.

Pathomorphology

In the acute period of the disease, a biopsy of the lymph nodes determines the proliferation of reticular and lymphoid tissue with the formation of large mononuclear cells and circulatory disorders. At the same time, Kupffer cell hyperplasia and, in some cases, focal and widespread necrosis are detected. Similar histological changes are noted in the tonsils and peritonsillar tissue. In the spleen, hyperplasia of the follicles, edema and infiltration of its capsule by mononuclear cells are observed. In the liver, in severe forms of infectious mononucleosis, there is deposition of bile pigment in the hepatocytes of the central zones of the lobules. The detection of wide-plasma mononuclear cells in the lungs, spleen, kidneys, and central nervous system indicates that proliferation of lymphoreticular tissue is observed in various organs.

2. Classification of infectious mononucleosis

By type: 1. Typical

2. Atypical

Erased

Asymptomatic

By severity:

1. Light form

2. Medium-heavy

3. Heavy

Severity criteria

Severity of intoxication syndrome

Expression of local changes

By flow (by character):

1) Smooth

2) Unsmooth

With complications

With a layer of secondary infection

With exacerbation chronic diseases

3. Clinical picture of infectious mononucleosis

The incubation period varies from 5 days to 1.5 months. There may be a prodromal period without specific symptoms. In these cases, the disease develops gradually: subfebrile body temperature, malaise, weakness, increased fatigue, catarrhal phenomena in the upper respiratory tract - nasal congestion, hyperemia of the mucous membrane of the oropharynx, enlargement and hyperemia of the tonsils.

With the acute onset of the disease, body temperature quickly rises to high levels. Patients complain about headache, sore throat when swallowing, chills, increased sweating, body aches. In the future, the temperature curve may be different; The duration of fever varies from several days to 1 month or more.

By the end of the first week of the disease, the peak period of the disease develops. The appearance of all the main clinical syndromes is characteristic: general toxic phenomena, tonsillitis, lymphadenopathy, hepatolienal syndrome. The patient’s health is deteriorating, it is noted high temperature body, chills, headache and body aches. Nasal congestion with difficulty in nasal breathing and a nasal voice may appear. Lesions of the pharynx are manifested by an increase in sore throat, the development of sore throat in catarrhal, ulcerative-necrotic, follicular or membranous form. Hyperemia of the mucous membrane is not clearly expressed, loose yellowish plaques that can be easily removed appear on the tonsils. In some cases, plaques may resemble diphtheria. Hemorrhagic elements may appear on the mucous membrane of the soft palate; the posterior wall of the pharynx is sharply hyperemic, loose, granular, with hyperplastic follicles.

From the very first days, lymphadenopathy develops. Enlarged lymph nodes can be found in all areas accessible to palpation; Their lesions are characterized by symmetry. Most often with mononucleosis, the occipital, submandibular and especially posterior cervical lymph nodes on both sides along the sternocleidomastoid muscles are enlarged. Lymph nodes are compacted, mobile, painless or slightly painful on palpation. Their sizes vary from pea to walnut. The subcutaneous tissue around the lymph nodes may be swollen in some cases.

In most patients, during the height of the disease, an enlargement of the liver and spleen is noted. In some cases, icteric syndrome develops: dyspeptic symptoms intensify (decreased appetite, nausea), urine darkens, icterus appears in the sclera and skin, bilirubin content in the blood serum increases and aminotransferase activity increases.

Sometimes an exanthema of a maculopapular nature appears. It has no specific localization, is not accompanied by itching and quickly disappears without treatment, leaving no changes on the skin.

Following the period of the height of the disease, which lasts on average 2-3 weeks, a period of convalescence begins. The patient’s well-being improves, body temperature normalizes, and sore throat and hepatolienal syndrome gradually disappear. Subsequently, the size of the lymph nodes is normalized. The duration of the convalescence period varies from person to person, sometimes low-grade fever bodies and lymphadenopathy persist for several weeks.

The disease can take a long time, with alternating periods of exacerbations and remissions, which is why its total duration can last up to 1.5 years.

Clinical manifestations infectious mononucleosis at adults sick differ near features.

The disease often begins with the gradual development of prodromal phenomena, fever often persists for more than 2 weeks, the severity of lymphadenopathy and tonsil hyperplasia is less than in children. However, in adults, manifestations of the disease associated with involvement of the liver in the process and the development of icteric syndrome are more often observed.

Complications infectious mononucleosis

The most common complication is the addition of bacterial infections caused by Staphylococcus aureus, streptococci, etc. Meningoencephalitis, obstruction are also possible upper sections respiratory tract with enlarged tonsils. In rare cases, bilateral interstitial infiltration of the lungs with severe hypoxia, severe hepatitis (in children), thrombocytopenia, and splenic ruptures are noted. In most cases, the prognosis of the disease is favorable.

Differentialdiagnostics:

Infectious mononucleosis should be distinguished from lymphogranulomatosis and lymphocytic leukemia, tonsillitis of coccal and other etiologies, oropharyngeal diphtheria, as well as viral hepatitis, pseudotuberculosis, rubella, toxoplasmosis, chlamydial pneumonia and ornithosis, some forms adenovirus infection, CMV infections, primary manifestations HIV infections. Infectious mononucleosis is distinguished by a combination of the main five clinical syndromes: general toxic phenomena, bilateral tonsillitis, polyadenopathy (especially with damage to the lymph nodes along the sternocleidomastoid muscles on both sides), hepatolienal syndrome, and specific changes in the hemogram. In some cases, jaundice and (or) maculopapular exanthema are possible.

4. Laboratory diagnosis of infectious mononucleosis

The most characteristic sign is changes cellular composition blood. The hemogram reveals moderate leukocytosis, relative neutropenia with a shift in the leukocyte formula to the left, a significant increase in the number of lymphocytes and monocytes (over 60% in total). In the blood there are atypical mononuclear cells - cells with wide basophilic cytoplasm, having different shapes. Their presence in the blood determined modern name diseases. An increase in the number of atypical mononuclear cells with wide cytoplasm to at least 10-12% is of diagnostic significance, although the number of these cells can reach 80-90%. It should be noted that the absence of atypical mononuclear cells in the characteristic clinical manifestations of the disease does not contradict the expected diagnosis, since their appearance in the peripheral blood may be delayed until the end of the 2-3rd week of the disease.

During the period of convalescence, the number of neutrophils, lymphocytes and monocytes gradually normalizes, but quite often atypical mononuclear cells persist for a long time.

Virological diagnostic methods (isolation of the virus from the oropharynx) are not used in practice. PCR can detect viral DNA in whole blood and serum.

Developed serological methods determination of antibodies of various classes to capsid (VCA) antigens. Serum IgM to VCA antigens can be detected already during the incubation period; subsequently they are detected in all patients (this serves as reliable confirmation of the diagnosis). IgM to VCA antigens disappear only 2-3 months after recovery. After an illness, IgG to VCA antigens remain for life.

In the absence of the ability to detect anti-VCA-IgM, serological methods for detecting heterophilic antibodies are still used. They are formed as a result of polyclonal activation of B lymphocytes. The most popular are the Paul-Bunnell reaction with sheep erythrocytes (diagnostic titer 1:32) and the more sensitive Hoff-Bauer reaction with horse erythrocytes. Insufficient specificity of reactions reduces their diagnostic value.

All patients with infectious mononucleosis or if it is suspected should be tested 3 times (in the acute period, then after 3 and 6 months) laboratory examination for antibodies to HIV antigens, since mononucleosis-like syndrome is also possible during the stage of primary manifestations of HIV infection.

5. Treatment

Patients with mild and moderate forms of infectious mononucleosis can be treated at home

Bed rest for the entire acute period.

Diet: liquid and semi-liquid recommended dairy-vegetable food, rich in vitamins, extra drink ( cranberry juice, tea with lemon, compote) and fruits. In cases of illness with manifestations of hepatitis, a diet is recommended (table No. 5).

Drugs are used as etiotropic therapy for moderate and severe forms of the disease. recombinant interferon(viferon) and its inducers (cycloferon, neovir).

Specific therapy has not been developed. Detoxification therapy, desensitizing therapy (claritin, pipolfen, suprastin), symptomatic and restorative treatment, and rinsing the oropharynx with antiseptic solutions are carried out. According to indications, hepatoprotectors are prescribed (LIV-52, Essentiale, Karsil).

Antibiotics are not prescribed in the absence of bacterial complications. In case of hypertoxic course of the disease, as well as in case of threat of asphyxia caused by swelling of the pharynx and pronounced enlargement of the tonsils, a short course of treatment with glucocorticoids is prescribed (oral prednisolone in a daily dose of 1-1.5 mg/kg for 3-4 days).

Local treatment includes instillation of naphthyzine, galazolin, adrenaline-furacillin drops, protargol, sodium sulfacyl into the nose.

6. Modern approaches to Epstein treatment Barr-viral infections

According to many researchers, treatment of EBVI-mononucleosis (EBVIM) does not require specific therapy. Treatment of patients is usually carried out on an outpatient basis; patient isolation is not required. Indications for hospitalization should include prolonged fever, severe tonsillitis syndrome and/or tonsillitis syndrome, polylymphadenopathy, jaundice, anemia, airway obstruction, abdominal pain and the development of complications (surgical, neurological, hematological, cardiovascular and respiratory system, syndrome Reye).

In case of mild and moderate course of EBV MI, it is advisable for patients to recommend a ward or general mode welcome back to ordinary activities at an adequate physical and energetic level for each specific patient. A multicenter study showed that unreasonably recommended strict bed rest prolongs the recovery period and is accompanied by a long-term asthenic syndrome, often requiring drug treatment.

In mild cases of EBV MI, treatment of patients is limited to supportive therapy, including adequate hydration, rinsing the oropharynx with an antiseptic solution (with the addition of a 2% solution of lidocaine (xylocaine) for severe discomfort in the throat), non-steroidal anti-inflammatory drugs such as paracetamol (Acetaminophen, Tylenol). According to a number of authors, the prescription of H2 receptor blockers, vitamins, hepatoprotectors and local treatment of the tonsils with various antiseptics are ineffective and unfounded methods of treatment. Of the exotic methods of treatment, mention should be made of those recommended by F.G. Bokov et al. (2006) the use of megadoses of bifidobacteria in the treatment of patients with acute mononucleosis.

Opinions on the appropriateness of the appointment antibacterial drugs in the treatment of EBVIM are very controversial. According to Gershburg E. (2005), tonsillitis in MI is often aseptic and the prescription of antibacterial therapy is not justified. There is also no point in using antibacterial agents for catarrhal tonsillitis. The indication for prescribing antibacterial drugs is the addition of a secondary bacterial infection(development of lacunar or necrotizing tonsillitis in the patient, complications such as pneumonia, pleurisy, etc.), as evidenced by pronounced inflammatory changes in blood counts and febrile fever persisting for more than three days. The choice of drug depends on the sensitivity of the microflora on the patient’s tonsils to antibiotics and possible adverse reactions from organs and systems.

In patients, hemophilus influenzae, staphylococcus and streptococcus pyogenes are more often isolated, less often - fungi of the genus Candida], therefore it should be considered justified to prescribe to these patients drugs from the group of 2-3 generation cephalosporins, lincosamides, macrolides and antifungal agents (fluconazole) in therapeutic doses for 5 -7 days (less often - 10 days). Some authors, in the presence of necrotizing tonsillitis and putrid smell from the mouth, probably caused by associated anaerobic flora, it is recommended to use metronidazole 0.75 g / day, divided into 3 doses, for 7-10 days.

Contraindicated drugs from the group of aminopenicillins (ampicillin, amoxicillin (Flemoxin Solutab, Hiconcil), amoxicillin with clavulanate (Amoxiclav, Moksiclav, Augmentin)) due to the possibility of developing allergic reaction in the form of exanthema. The appearance of a rash to aminopenicillins is not an IgE-dependent reaction, therefore the use of H1 histamine receptor blockers has neither a preventive nor a therapeutic effect.

According to a number of authors, the empirical approach to prescribing glucocorticosteroids to patients with EBVI is still maintained. Glucocorticosteroids (prednisolone, prednisone (Deltazone, Meticorten, Orazon, Liquid Pred), Solu Cortef (hydrocortisone), dexamethasone) are recommended for patients with severe EBVIM, airway obstruction, neurological and hematological complications (severe thrombocytopenia, hemolytic anemia). The daily dose of prednisolone is 60-80 mg for 3-5 days (less often 7 days), followed by rapid discontinuation of the drug. There is no identical point of view on prescribing glucocorticosteroids to these patients with the development of myocarditis, pericarditis and central nervous system lesions.

In severe cases of EBVIM, intravenous detoxification therapy is indicated; in case of splenic rupture, surgical treatment is indicated.

The most controversial issue remains about prescribing antiviral therapy for patients with EBVI. Currently, a large list of drugs is known that are inhibitors of EBV replication in cell culture.

All modern "candidates" For treatment EBVI can be separated on two groups:

I. Suppressing the activity of EBV DNA polymerase:

Acyclic nucleoside analogues (acyclovir, ganciclovir, penciclovir, valacyclovir, valganciclovir, famciclovir);

Acyclic nucleotide analogues (cidofovir, adefovir);

Pyrophosphate analogues (Foscarnet (foscavir), phosphonoacetylic acid);

4 oxo-dihydroquinolines (possibly).

II. Various compounds that do not inhibit viral DNA polymerase (mechanism under study): maribavir, beta-L-5 uracil iododioxolane, indolocarbazole.

However, a meta-analysis of five randomized controlled trials involving 339 EBVIM patients taking acyclovir (Zovirax) showed the drug to be ineffective.

One of possible reasons lies in the development cycle of EBV, in which the DNA of the virus has a linear or circular (episome) structure and multiplies in the nucleus of the host cell. Active replication of the virus occurs during the productive (lytic) stage of the infectious process (EBV DNA of linear form). With acute EBVI and activation of chronic EBVI, a cytolytic cycle of virus development occurs, during which it triggers the expression of its own early antigens and activates some genes of the host cells, the products of which are involved in the replication of EBV. In latent EBVI, the DNA of the virus has the form of an episome (circular supercoiled genome) located in the nucleus. The circular DNA genome of EBV is characteristic of CD21+ lymphocytes, in which, even during primary infection with the virus, the lytic stage of the infectious process is practically not observed, and the DNA is reproduced in the form of an episome synchronously with the cell division of infected cells. The death of EBV-affected B lymphocytes is not associated with virus-mediated cytolysis, but with the action of cytotoxic lymphocytes.

When prescribing antiviral drugs for EBVI, the doctor must remember that they clinical effectiveness depends on the correct interpretation of the clinical manifestations of the disease, the stage of the infectious process and the development cycle of the virus at this stage. However, no less important is the fact that most of the symptoms of EBV are associated not with the direct cytopathic effect of the virus in infected tissues, but with the indirect immunopathological response of EBV-infected B lymphocytes circulating in the blood and located in the cells of the affected organs. That is why nucleoside analogues (acyclovir, ganciclovir, etc.) and polymerase inhibitors (Foscarnet), which suppress EBV replication and reduce the virus content in saliva (but do not completely sanitize it, do not have a clinical effect on the severity and duration of EBVIM symptoms.

Indications for the treatment of EBVIM with antiviral drugs are: severe, complicated course of the disease, the need to prevent EBV-associated B-cell lymphoproliferation in immunocompromised patients, EBV-associated leukoplakia. It is recommended to use acyclovir (Zovirax) orally at a dose of 800 mg orally 5 times a day for 10 days (or 10 mg/kg every 8 hours for 7-10 days). For lesions of the nervous system it is preferable intravenous method administration of the drug at a dose of 30 mg/kg/day 3 times a day for 7-10 days.

According to Gershburg, (2005), if under the influence of any factors (for example, immunomodulators, in EBV-associated malignant tumors - the use of radiation therapy, gemcitabine, doxorubicin, arginine butyrate, etc.) it is possible to transfer EBV DNA from the episome to the active replicative form, i.e. activate the lytic cycle of the virus, then in this case a clinical effect from antiviral therapy can be expected.

In recent years, recombinant alpha interferons (Intron A, Roferon-A, Reaferon-EC) at a dose of 1 million IU intramuscularly for 5-7 days or every other day have become increasingly used for the treatment of EBVI; for chronic active EBVI - 3 million IU intramuscularly 3 times a week, course 12-36 weeks.

As an interferon inducer in severe cases of EBVI, it is recommended to use Cycloferon 250 mg (12.5% 2.0 ml) IM, 1 time per day, No. 10 (the first two days daily, then every other day) or according to the scheme: 250 mg/day, IM on the 1st, 2nd, 4th, 6th, 8th, 11th, 14th, 17th, 20th, 23rd, 26th 1st and 29th day in combination with etiotropic therapy. Orally, Cycloferon is prescribed at 0.6 g/day, course dose (6-12 g, i.e. 20-40 tablets).

Drug correction of asthenic syndrome in chronic EBVI includes the administration of adaptogens, high doses of B vitamins, nootropic drugs, antidepressants, psychostimulants, drugs with a procholinergic mechanism of action and correctors of cellular metabolism.

Collateral successful treatment a patient with EBVI is complex therapy and strictly individual management tactics both in the hospital and during dispensary observation.

Conclusion

Thus, inclusion in complex therapy children with infectious mononucleosis, preparations of recombinant alpha 2b-interferon Reaferon -EC- Lipinta, Viferon, Kipferon are accompanied by positive clinical and hematological changes, more pronounced when using the liposomal form of interferon alpha. However, the administration of Viferon and Kipferon in the form rectal suppositories gave many children an unpleasant feeling. Therefore, the more physiological oral use of Reaferon-EC-Lipint is preferable.

References

1. E.M. Klimanova, G.D. Guseva, E.N. Kurnosenok, O.S. Zotova, S.A. Guy; Reaferon-ES-Lipint in the treatment of children with infectious mononucleosis // Journal "Polyclinic" No. 4 (1) 2011, pp. 44-45.

2. A.P. Kudin; Some issues in the treatment of infectious mononucleosis in children // Medical Journal; 2012 No. 3, pp. 138-143.

3. V.N. Timchenko and L.V. Bystryakov // Infectious diseases in children: Textbook for pediatric faculties of medical universities. St. Petersburg: SpetsLit, 2001. p. 197.

4. N.M. Shvedova, E.V. Mikhailova, Yu.S. Tseka, T.K. Chudakova: Infectious mononucleosis in children: Clinical and laboratory justification and economic efficiency of the use of immunocorrectors // Saratov Scientific and Medical Journal; 2013: T 9: No. 3 pp. 512-517.

5. I.V. Shestakova, N.D. Yushchuk Modern approaches to the treatment of Epstein-Barr virus infection in adults//Attending physician. 2011. No. 2: pp. 98-103.

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INFECTIOUS MONONUCLEOSIS

Performed by a student of the Faculty of Medicine

Specialties

"Medicine"

Rate: 508 p/y

Amirmetova Elvira Shamil kyzy

Nalchik

Infectious mononucleosis (mononucleosis infectiosa, Filatov's disease, monocytic tonsillitis, benign lymphoblastosis)- an acute viral disease that is characterized by fever, damage to the pharynx, lymph nodes, liver, spleen and peculiar changes in blood composition.

Story

The infectious nature of this disease was pointed out by N. F. Filatov in 1887, who was the first to draw attention to a febrile disease with enlarged lymph nodes and called it idiopathic inflammation of the lymph glands. The described disease bore his name for many years - Filatov's disease. In 1889, the German scientist Emil Pfeiffer described a similar clinical picture of the disease and defined it as glandular fever affecting the pharynx and lymphatic system. With the introduction of hematological research into practice, characteristic changes in blood composition in this disease were studied, according to which American scientists T. Sprunt and F. Evans called the disease infectious mononucleosis. In 1964, M.A. Epstein and I. Barr isolated a herpes-like virus from Burkitt's lymphoma cells, named in their honor the Epstein-Barr virus, which was later found with great consistency in infectious mononucleosis.

Epidemiology

The epidemiological picture of infectious mononucleosis is as follows: the disease is recorded everywhere, and, as a rule, these are episodic cases or isolated outbreaks of infection. The heterogeneity of clinical manifestations and the often encountered problems with establishing a diagnosis suggest that the official incidence figures do not correspond to the real picture of the spread of infectious mononucleosis. Most often, teenagers suffer from this disease, with girls getting sick earlier - at 14-16 years old, boys later - at 16-18. It is for this reason that another name for the disease has spread – “student disease”. People who have crossed the forty-year mark do not get sick often, but carriers of HIV infection are at risk of activating a dormant infection throughout their lives. If a person becomes infected with infectious mononucleosis at an early age, the disease resembles a respiratory infection, but the older the patient, the more likely it is that there will be no clinical symptoms. After thirty years, almost all people have antibodies to the causative agent of infectious mononucleosis, hence the rarity of obvious forms of the disease among adults. The incidence almost does not depend on the time of year; slightly fewer cases are recorded in the summer. Factors that increase the risk of infection are crowded conditions, the use of common household items, and household disorder.

Epidemiology

Source of infection is a sick person and a virus carrier.

Transmission of infection occurs by airborne droplets. Due to the fact that the infection is transmitted mainly through saliva (by kissing), the disease is called "kissing disease". Transmission mechanism infections - aerosol. Transmission of infection through blood transfusion is possible. The crowding of sick and healthy people creates a risk group in places of residence such as dormitories, boarding schools, kindergartens, camps, etc.

The maximum incidence of MI in girls is observed at the age of 14-16 years, in boys 17-18 years. As a rule, by the age of 25-35, most people have antibodies to the IM virus in their blood when examined. It is worth noting that in HIV-infected people, reactivation of the virus can occur at any age.

Etiology.

The causative agent of the infection is the DNA-containing Epstein-Barr virus. This virus is able to replicate in B lymphocytes and, unlike other herpes viruses, it activates cell proliferation.

Epstein-Barr virus virions include specific antigens (AG):

Capsid Ag (VCA)

Nuclear AG (EBNA)

Early hypertension (EA)

Membrane AG (MA)

Antibodies to the capsid antigen (VCA) first appear in the blood of patients with infectious mononucleosis. Antibodies to membrane (MA) and early (EA) antigens are produced later. The infectious agent is poorly resistant to the external environment and quickly dies when it dries out, under the influence of high temperature and disinfectants. Epstein-Barr virus can also cause Burkitt's lymphoma and nasopharyngeal carcinoma.

Pathogenesis.

The severity of immunological reactions during infectious mononucleosis allows us to consider it a disease of the immune system, therefore it is classified as a group of diseases of the AIDS-associated complex.

Clinic.

Incubation period varies from 5 days to 1.5 months. A prodromal period without specific symptoms is possible. In these cases, the disease develops gradually: within a few days, low-grade body temperature, malaise, weakness, increased fatigue, catarrhal phenomena in the upper respiratory tract - nasal congestion, hyperemia of the mucous membrane of the oropharynx, enlargement and hyperemia of the tonsils are observed. At the acute onset of the disease body temperature quickly rises to high levels. Patients complain of headache, sore throat when swallowing, chills, increased sweating, and body aches. In the future, the temperature curve may be different; The duration of fever varies from several days to 1 month or more. By the end of the first week of the disease, the peak period of the disease develops. The appearance of all the main clinical syndromes is characteristic: general toxic phenomena, tonsillitis, lymphadenopathy, hepatolienal syndrome. The patient’s health deteriorates; high body temperature, chills, headache and body aches are noted. Nasal congestion with difficulty in nasal breathing and a nasal voice may appear. Lesions of the pharynx are manifested by an increase in sore throat, development of sore throat in catarrhal, ulcerative-necrotic, follicular or membranous form. Hyperemia of the mucous membrane is not clearly expressed, loose yellowish plaques that can be easily removed appear on the tonsils. In some cases, plaques may resemble diphtheria. Hemorrhagic elements may appear on the mucous membrane of the soft palate; the posterior wall of the pharynx is sharply hyperemic, loose, granular, with hyperplastic follicles. From the very first days it develops lymphadenopathy. Enlarged lymph nodes can be found in all areas accessible to palpation; Their lesions are characterized by symmetry. Most often with mononucleosis, the occipital, submandibular and especially posterior cervical lymph nodes on both sides along the sternocleidomastoid muscles are enlarged. Lymph nodes are compacted, mobile, painless or slightly painful on palpation. Their sizes vary from pea to walnut. The subcutaneous tissue around the lymph nodes may be swollen in some cases. In most patients, during the height of the disease, an enlargement of the liver and spleen is noted. In some cases, icteric syndrome develops: dyspeptic symptoms intensify (decreased appetite, nausea), urine darkens, icterus appears in the sclera and skin, bilirubin content in the blood serum increases and aminotransferase activity increases. Sometimes an exanthema of a maculopapular nature appears. It has no specific localization, is not accompanied by itching and quickly disappears without treatment, leaving no changes on the skin. Following the period of the height of the disease, which lasts an average of 2-3 weeks, comes convalescence period. The patient’s well-being improves, body temperature normalizes, and sore throat and hepatolienal syndrome gradually disappear. Subsequently, the size of the lymph nodes is normalized. The duration of the convalescence period varies from person to person; sometimes low-grade body temperature and lymphadenopathy persist for several weeks. The disease can take a long time, with alternating periods of exacerbations and remissions, which is why its total duration can last up to 1.5 years. Clinical manifestations of infectious mononucleosis in adult patients differ in a number of features. The disease often begins with the gradual development of prodromal phenomena, fever often persists for more than 2 weeks, the severity of lymphadenopathy and tonsil hyperplasia is less than in children. At the same time, in adults, manifestations of the disease associated with involvement of the liver in the process and the development of icteric syndrome are more often observed. Complications.

The most common complication is the addition of bacterial infections caused by Staphylococcus aureus, streptococci, etc. Meningoencephalitis and obstruction of the upper respiratory tract by enlarged tonsils are also possible. In rare cases, bilateral interstitial infiltration of the lungs with severe hypoxia, severe hepatitis (in children), thrombocytopenia, and splenic ruptures are noted. In most cases, the prognosis of the disease is favorable.

Diagnostics.

Infectious mononucleosis should be distinguished from lymphogranulomatosis and lymphocytic leukemia, tonsillitis of coccal and other etiologies, oropharyngeal diphtheria, as well as viral hepatitis, pseudotuberculosis, rubella, toxoplasmosis, chlamydial pneumonia and ornithosis, some forms of adenoviral infection, CMV infection, primary manifestations of HIV infection . Infectious mononucleosis is distinguished by a combination of the main five clinical syndromes: general toxic phenomena, bilateral tonsillitis, polyadenopathy (especially with damage to the lymph nodes along the sternocleidomastoid muscles on both sides), hepatolienal syndrome, and specific changes in the hemogram. In some cases, jaundice and (or) maculopapular exanthema are possible. Laboratory diagnostics

The most characteristic sign is changes in the cellular composition of the blood. The hemogram reveals moderate leukocytosis, relative neutropenia with a shift in the leukocyte formula to the left, a significant increase in the number of lymphocytes and monocytes (over 60% in total). In the blood there are atypical mononuclear cells - cells with wide basophilic cytoplasm, having different shapes. Their presence in the blood determined the modern name of the disease. An increase in the number of atypical mononuclear cells with wide cytoplasm to at least 10-12% is of diagnostic significance, although the number of these cells can reach 80-90%. It should be noted that the absence of atypical mononuclear cells in the characteristic clinical manifestations of the disease does not contradict the expected diagnosis, since their appearance in the peripheral blood may be delayed until the end of the 2-3rd week of the disease. During the period of convalescence, the number of neutrophils, lymphocytes and monocytes gradually normalizes, but quite often atypical mononuclear cells persist for a long time. Virological diagnostic methods (isolation of the virus from the oropharynx) are not used in practice. PCR can detect viral DNA in whole blood and serum. Serological methods have been developed for the determination of antibodies of various classes to capsid (VCA) antigens. Serum IgM to VCA antigens can be detected already during the incubation period; subsequently they are detected in all patients (this serves as reliable confirmation of the diagnosis). IgM to VCA antigens disappear only 2-3 months after recovery. After an illness, IgG to VCA antigens remain for life. In the absence of the ability to detect anti-VCA-IgM, serological methods for detecting heterophilic antibodies are still used. They are formed as a result of polyclonal activation of B lymphocytes. The most popular are the Paul-Bunnell reaction with sheep erythrocytes (diagnostic titer 1:32) and the more sensitive Hoff-Bauer reaction with horse erythrocytes. Insufficient specificity of reactions reduces their diagnostic value. All patients with infectious mononucleosis or suspected of having it should undergo three laboratory tests (in the acute period, then after 3 and 6 months) for antibodies to HIV antigens, since mononucleosis-like syndrome is also possible at the stage of primary manifestations of HIV infection.

Differential diagnosis.

In the typical course of infectious mononucleosis, its diagnosis does not cause much difficulty and is based on a clinical examination and analysis results, taking into account epidemiological data and the results of a serological study. There is often a need to differentiate it from diseases in which tonsil damage, lymphadenitis, and fever are observed.

Often, at the onset of infectious mononucleosis, a diagnosis of tonsillitis is made. An acute onset with fever and reaction of the lymph nodes gives rise to this. But unlike infectious mononucleosis, in patients with tonsillitis the leading complaint is a sore throat, inflammatory changes in the palatine tonsils are pronounced from the 1st day, regional lymphadenitis develops, and not widespread lymphadenopathy. Diagnostic doubts are resolved by detectable neutrophilic leukocytosis.

Diphtheria of the pharynx may be mistakenly suspected in cases of infectious mononucleosis. Severe consequences occur when diphtheria of the pharynx is mistaken for infectious mononucleosis and, therefore, appropriate treatment is not carried out. The combination of sore throat with general intoxication, fever and lymphadenitis is characteristic of both infections. But with diphtheria of the pharynx, by the end of the 1st day, a gray-white or dirty-gray fibrinous plaque protruding above the surface of the mucous membrane is detected on the enlarged, moderately hyperemic tonsils. When you try to remove it, bleeding occurs. Low-grade or high temperature, general intoxication, increasing, with the transition of a localized form to a widespread one or expressed from the very beginning with toxic diphtheria. Regional lymph nodes are somewhat enlarged, painful, and are surrounded by soft, painless swelling of the subcutaneous base. In patients with infectious mononucleosis, in the first days of the disease there is only slight redness and swelling of the tonsils and the surrounding mucous membrane of the pharynx. Tonsillitis develops at different times, but more often at a later stage; plaque can also spread beyond the tonsils, but is easily removed, and its color is yellowish. Not only regional but also more distant lymph nodes become enlarged; generalized lymphadenitis, hepato- and splenomegaly often occur. General intoxication is moderate. Lymphocytes and monocytes predominate in the blood, and the number of mononuclear cells increases. ESR is normal, unlike accelerated in diphtheria.

Of great importance for the final diagnosis are the results of bacteriological examination of films for the presence of the causative agent of diphtheria, data from the Paul-Bunnell reaction and the study of the epidemiological situation.

Adenovirus infection, which occurs with tonsillitis syndrome, is in many ways similar to infectious mononucleosis. With both nosological forms, polyadenitis, hepatolienal syndrome, mild intoxication, prolonged fever and signs of respiratory tract damage are possible. The latter are more pronounced in case of adenoviral infection, the exudative component is significant, and adenoviral antigen is detected in swabs from the nasal pharynx using immunofluorescence. Sometimes a typical combination of symptoms and epidemiological history data about the spread of infection in children or youth groups with a significant number of conjunctivitis among the sick help to establish a diagnosis. In patients with adenovirus infection general analysis blood without significant changes, in contrast to the typical hemogram picture in infectious mononucleosis;

Rubella can be mistaken for infectious mononucleosis with severe lymphadenopathy and scanty exanthema. In such cases, one should take into account the predominant enlargement of the occipital and posterior cervical lymph nodes, a slight increase in temperature, the absence of pathological changes in the pharynx, the short duration of the disease, the presence of leukopenia, lymphocytosis, plasma cells, as well as a negative Paul-Bunnel-Davidson reaction.

At mumps, usually accompanied by a temperature reaction, symptoms of general intoxication and deformation in the parotid and submandibular areas, sometimes at first there is a need for differential diagnosis with infectious mononucleosis. Important distinguishing features are localization, the nature of local changes and the general reaction. The manifest sign of mumps is damage to the salivary glands, mainly the parotid glands, sometimes the submandibular and sublingual glands with a typical deformation between the earlobe and the ascending ramus of the mandible, usually on two sides, less often on one side. In this case, there is always swelling of the surrounding subcutaneous base, its boundaries are unclear, the consistency is doughy, and it is painful on palpation. When opening the mouth, talking and chewing, pain occurs, radiating to the ear, and is combined with dry mouth. The lymph nodes in this area are normal or slightly enlarged. Intoxication is pronounced from the first days, and meningeal syndrome is often detected. Positive symptoms of Filatov (pain behind the earlobe) and Murson (infiltration and hyperemia of the parotid duct area). For infectious mononucleosis; enlarged lymph nodes, predominantly generalized lymphadenopathy, are determined. Pain when swallowing is not combined with dry mouth, Murson's sign is negative. The presence of changes in the leukocyte blood count that are atypical for infectious mononucleosis and epidemiological data resolve diagnostic doubts.

Serum sickness is manifested by some clinical symptoms that are also observed with infectious mononucleosis: rash, fever, polyadenitis, leukocytosis or leukopenia with lymphomonocytosis. Important in resolving the issue is information about the administration of serum drugs to the patient; The rash is often urticarial, itchy, there is often pain and swelling in the joints, eosinophilia in the absence of mononuclear cells in the blood. Since in serum sickness, as in infectious mononucleosis, the Paul-Bunnell reaction can detect heterophilic antibodies, for the purpose of differential diagnosis the Paul-Bunnell-Davidson reaction should be used.

Sometimes it becomes necessary to distinguish between lymphogranulomatosis in the initial period and infectious mononucleosis, especially in the case of primary localization of the process in the neck. In contrast to infectious mononucleosis, in lymphogranulomatosis, the lymph nodes reach large sizes, are painless, elastic at first, and subsequently become dense and merge with each other, forming tumor-like conglomerates that are not fused to the skin. Over time, more and more lymph nodes are involved in the process. Changes appear in internal organs. Damage to the lymph nodes against the background of fever is combined with increased sweating and skin itching, making up a triad of symptoms characteristic of lymphogranulomatosis. In the blood, often against the background of leukocytosis, in contrast to infectious mononucleosis, lymphopenia and a shift of the leukocyte formula to the left to band neutrophilic granulocytes are determined; sometimes young and myelocytes. In the initial stage and during exacerbation, eosinophilia is often detected. A characteristic hematological sign of lymphogranulomatosis is a significant increase in ESR, in contrast to the moderate increase in infectious mononucleosis; In difficult cases, the final diagnosis is decided taking into account serological data and the results of histological examination of lymph nodes or punctates.

Infectious oligosymptomatic lymphocytosis is a little-known, rare disease. Unlike infectious mononucleosis, it is detected in children, less often in adults during preventive examinations, it is characterized by a slight change in well-being, the absence of enlargement of the lymph nodes, liver and spleen, is not accompanied by an increase in temperature, and a short-term low-grade fever is rarely observed. Diagnostic doubts are resolved by the blood picture. In infectious lymphocytosis, an increase in the number of lymphocytes with a monomorphic composition in combination with hyperleukocytosis and eosinophilia is determined. The content of small and medium lymphocytes reaches 0.8-0.95, whereas with infectious mononucleosis; Cellular polymorphism comes to the fore, an increased content of all types of mononuclear cells is recorded, the number of small lymphocytes is reduced.

The severe course of infectious mononucleosis sometimes clinically resembles leukemia. The similarities are the presence of sore throat, fever, leukocytosis, enlarged lymph nodes and spleen. Leukemic mononuclear cells may be mistaken for atypical ones. The absence of cyclicity in the development of the disease, progressive deterioration of the general condition, pallor of the mucous membranes and skin, moderation of the febrile reaction, and hemorrhages indicate leukemia. In this case, enlarged lymph nodes do not predominate in the clinical picture of the disease. Leukocytosis is usually significant (up to 100*109/l or more), anemia and thrombocytopenia are noted. Data from sternal puncture resolve the issue of diagnosis.

In visceral forms of infectious mononucleosis, diagnostic difficulties often arise. Respiratory forms of the disease that occur influenza-like or in the form of pneumonia are difficult to distinguish from influenza, other acute respiratory infections and forms complicated by acute pneumonia only on the basis of anamnesis and objective data. For infectious mononucleosis; with the development of syndromes of eado-, myo- or pericarditis, digestive forms (mesoadenitis, appendiceal syndrome, pancreatitis, etc.), as well as in cases with predominant damage to the nervous system (meningitis, meningoencephalitis, etc.), clinical manifestations are identical to the named syndromes of other etiologies . Hepatic forms, manifested by jaundice, can be difficult to distinguish from viral hepatitis.

An important sign in the clinical recognition of visceral forms of infectious mononucleosis is generalized lymphadenopathy, which is not characteristic of the listed syndromes of other etiologies, especially its combination with damage to the tonsils. But the decisive importance in this case belongs to the characteristic hematological indicators (increase in the number of mononuclear cellular elements) and the results of serological studies. It is important to remember that in patients with viral hepatitis, as in infectious mononucleosis, it is possible to detect heterophilic antibodies in the blood serum. Therefore, in cases that are difficult for differential diagnosis, the Paul-Bunnell-Davidson reaction should be used from serological reactions, which makes it possible to clarify the origin of the detected heterophilic antibodies.

Treatment.

To date, there is no specific treatment for infectious mononucleosis in children, there is no single treatment regimen, and there is no antiviral drug that would effectively suppress the activity of the virus. Usually the disease is treated in a hospital setting; in severe cases, only bed rest is recommended. There are several areas of treatment for mononucleosis in children:

Therapy is mainly aimed at relieving the symptoms of infectious mononucleosis

Pathogenetic therapy in the form of antipyretics for children (Ibuprofen, Paracetamol in syrup)

Antiseptic local drugs for the relief of sore throat, as well as local nonspecific immunotherapy, are prescribed the drugs Imudon and IRS 19.

Desensitizing agents

General strengthening therapy - vitamin therapy, including vitamins B, C and P.

If changes in liver function are detected, a special diet, choleretic drugs, hepatoprotectors are prescribed

Immunomodulators together with antiviral drugs provide greatest effect. Imudon, Children's Anaferon, Viferon, as well as Cycloferon at a dose of 6-10 mg/kg can be prescribed. Sometimes metronidazole (Trichopol, Flagyl) has a positive effect.

Since secondary microbial flora is often associated, antibiotics are indicated, which are prescribed only in case of complications and intense inflammatory process in the oropharynx (except for penicillin antibiotics, which cause severe allergic reactions in 70% of cases in infectious mononucleosis)

During antibiotic therapy, probiotics are simultaneously prescribed (Acipol, Narine, Primadophilus for Children, etc. see the entire list of probiotic preparations with prices and composition)

In case of severe hypertoxicity, a short-term course of prednisolone is indicated (20-60 mg per day for 5-7 days), it is used if there is a risk of asphyxia

Installation of a tracheostomy and transfer to artificial ventilation is carried out in case of severe swelling of the larynx and difficulty breathing in children

If there is a threat of rupture of the spleen, a splenectomy is performed urgently

Prevention.

There is no specific immunoprophylaxis against infectious mononucleosis (vaccine prophylaxis). Since the route of infection is airborne, all preventive measures are similar to preventive measures for acute respiratory diseases. It is important to remember that the virus will not be able to “thrive” in a body with a strong immune system, so you need to focus your efforts on strengthening your defenses. It is necessary to observe the rules of personal hygiene and avoid engaging in casual sexual relationships.

After contact of a child with a patient, emergency prevention should be carried out in the form of immunoglobulin. Where there are patients, constant wet cleaning and disinfection of the patient’s personal belongings are carried out.

Classification of infectious mononucleosis

I. International statistical classification of diseases X revision (ICD X)

B 27 - infectious mononucleosis;

At 27.0 - mononucleosis caused by the gammaherpetic virus;

B 27.1 - cytomegalovirus mononucleosis;

At 27.8 - another infectious mononucleosis;

At 27.9 - infectious mononucleosis, unspecified.

II. Clinical classification of MI.

1. Typical.
2. Atypical (asymptomatic, erased, visceral).

By severity:

1. Lightweight.
2. Moderate.
3. Heavy.

According to the nature of the flow:

1. Smooth.
2. Unsmooth: with complications, with a layer of secondary infection, with exacerbation of chronic diseases, with relapses.

By duration:

1. Acute (up to 3 months).
2. Prolonged (3-6 months).
3. Chronic (more than 6 months).

Clinical characteristics of infectious mononucleosis

The clinical manifestations of MI are extremely varied, depending on the age of the patients and the etiological factor, which makes timely diagnosis of the disease difficult. The onset of the disease can be acute (60-70%) or gradual. The virus persists in the body after latent or manifest MI for life. In this regard, in some cases, MI can take a chronic, relapsing course, and also transform into an immunodeficiency state.

The combination of tonsillitis, lymphadenopathy, enlarged liver, spleen and changes in white blood in the form of lymphocytosis and atypical mononuclear cells against the background of fever is a classic mononucleosis complex and is characteristic of MI. The incubation period of mononucleosis ranges from 20-50 days. Usually the disease begins with prodromal symptoms: weakness, myalgia, headache, chills, loss of appetite, and nausea. This condition can last from several days to 2 weeks and can be interpreted as a mononucleosis-like syndrome. Occurs with adenovirus infection, tonsillitis, pseudotuberculosis, chlamydia, HIV infection, and lymphoproliferative diseases. MI can take on the appearance of acute leukemia.

The most important differential diagnostic criterion for MI is the identification of six main clinical symptoms:

1) Fever and general intoxication (general intoxication syndrome).
2) Polyadenitis with predominantly enlarged cervical lymph nodes (lymphadenopathy syndrome.
3) Sore throat (angina syndrome: tonsillitis, adenoiditis).
4) Enlarged liver and spleen (hepatolienal syndrome).
5) Nasal congestion and nasal voice (respiratory syndrome: “dry nasopharyngitis”).

Most often, typical forms of infectious mononucleosis with a characteristic symptom complex develop with EBV-induced disease.

Lymphadenopathy is not only the main characteristic syndrome in MI, but also the most long-lasting, average duration which is 20 days. Patients complain more often of pain in the neck than in the throat, which is apparently due to acute increase lymph nodes of the neck. Cervical lymphadenitis most often observed along the entire length of the neck - from the submandibular to the lower cervical lymph nodes. The lymph nodes of other groups (subclavian, axillary, inguinal) increase less significantly.

Tonsillitis can be catarrhal, lacunar or ulcerative-necrotic with the formation of fibrinous films, which requires differential diagnosis with oropharyngeal diphtheria. Against the background of moderate hyperemia of the pharynx, there is an increase in the tonsils due to their pastiness, edema and infiltration with the presence of white, white-yellow or grayish deposits, mainly coming from the lacunae. Plaques on the tonsils last much longer than with bacterial sore throat. LN sizes of more than 2 cm are detected in half of the patients: clearly contoured, elastic, painless or slightly painful, mobile, multiple, sometimes in the form of “packets” or “chains”. Mainly the cervical lymph nodes are enlarged. The skin over them is not changed. Edema subcutaneous tissue there is no presence around them, but in 23% of children pastosity is detected. As a result of cervical lymphadenopathy, lymphostasis can be observed, which leads to puffiness of the face and pasty eyelids. In 2/3 of children, along with the inoculation of one or another microorganism, there is also an increase in antibody titers to it, which undoubtedly indicates the etiological role of the isolated microbes. Frequent occurrence acute tonsillitis during MI can be explained by the tropism of EBV to lymphoid tissue, a decrease in the local immunological reactivity of the tonsils involved in the production of antibodies. There is also evidence of the ability of EBV to block on the surface of the tonsils specific immunoglobulins, which leads to multiple adsorption of microorganisms on epithelial cells and massive bacterial colonization of the tonsils.

Adenoiditis

Adenoiditis is manifested by nasal congestion, difficulty in nasal breathing in the absence of nasal discharge, and snoring, especially during sleep. The patient's face takes on an “adenoid” appearance (puffiness of the face, pastiness of the eyelids, bridge of the nose, breathing through an open mouth, dry lips). During nasopharyngoscopy, enlargement and plaque on the pharyngeal tonsil, swelling of the inferior turbinate and nasopharyngeal mucosa are determined. Symptoms of adenoiditis usually persist for 5-10 days.

Nasal congestion and nasal voice, as a rule, are not accompanied by catarrhal symptoms. Tonsillitis comes in varying degrees of severity, from catarrhal to significant enlargement of the tonsils with the presence of loose yellowish-gray deposits in the lacunae. If tonsillitis is diagnosed, but the lymph nodes are not enlarged, this is not an MI.

Hepatomegaly is gradual, characterized by slight cytolysis. Jaundice is detected in 5-7% of patients. Hepatolienal syndrome is most pronounced by the tenth day from the onset of the disease. Liver damage is noted both in MI and may also occur isolated form EBV hepatitis with cholestasis syndrome.

Splenomegaly: the spleen often enlarges (in 50% of patients), but it is not always possible to palpate it. The spleen is dense, elastic, painless. When it increases significantly, a feeling of heaviness occurs in the left hypochondrium. Rough palpation can lead to its rupture. Splenic rupture is one of the most severe complications in MI.

A maculopapular rash occurs in 3-5% of patients with MI. Exanthema is most often caused by taking ampicillin or its analogues while prehospital stage, which is associated with excessive synthesis of antibodies of heterogeneous specificity, mainly of the IgM class. The reason for the formation of the rash is the adsorption of the resulting cyclic immune complexes (CIC) on the walls of small arterioles. Currently, there are studies that show that there is no connection between taking antibiotics and the development of rash in patients with MI. Most often, the rash is exudative in nature, less often - hemorrhagic, localized on the face, body, extremities, including palms and soles. The rash does not have any favorite localization. Exanthema appears on the 5-10th day of the disease, sometimes earlier - on the 1st-2nd day. The duration of the rash is usually about a week, sometimes more short time. Reverse development occurs gradually, peeling is possible. Some patients experience recurrent rashes, which are accompanied by eosinophilia and other hematological changes not related to the underlying disease.

Clinical manifestations of MI have some features depending on the age of the patients. For children under 3 years of age, the disease proceeds under the diagnosis of acute respiratory viral infection, without a sore throat, symptoms of rhinitis are not pronounced, “packets” of lymph nodes do not occur up to 1.5 years of age, and the duration of hepatolienal syndrome does not exceed a week.

The diagnosis is made on the basis of characteristic changes in the blood (lymphomonocytosis, the presence of atypical mononuclear cells).

From the blood side, the most characteristic sign of MI is the presence of atypical mononuclear cells (AM). In most cases, they are detected in the first days of the disease, especially at its height. In 40% of cases, AMs remain in the blood for up to one month or more. Early AMs are B lymphocytes immortalized by the virus. In subsequent stages of clinical manifestations, these are T cells. They are responsible for the lysis of infected B lymphocytes. The amount of AM in the blood of patients varies widely from 5-10 to 50% and higher.

Cytomegalovirus mononucleosis manifests itself with the same symptom complex as MI caused by EBV. The frequency of registration of CMV mononucleosis is 10-33% of all cases of infectious mononucleosis. CMV mononucleosis is characterized by high fever up to 39-40° With a duration of more than 2 weeks, signs of general intoxication, myalgia. Tonsillitis is characterized by the absence of plaque, lymphadenopathy is less likely to be generalized, liver enlargement is accompanied by a slight increase in transaminase activity, lymphocytosis with AM in CMV infection is less pronounced. Cytomegalovirus mononucleosis usually begins more suddenly than mononucleosis caused by the Epstein-Barr virus and resolves more slowly. It has been proven that up to 30% of hepatitis unknown etiology caused by liver damage from hepatitis B, mainly cytomegalovirus and herpes simplex virus. CMV hepatitis is severe with high activity and symptoms of cholestasis. Complications of cytomegalovirus mononucleosis are relatively rare and can manifest themselves in the form of interstitial or segmental pneumonia, pleurisy, myocarditis, arthritis, encephalitis, Guillain-Barré syndrome, which are accompanied by hepatosplenomegaly and pancytopenia. Reactivation of CMV leads to the development of sialoadenitis, hepatitis with a cholestatic component, interstitial pneumonia, esophagitis, enterocolitis, including ulcerative necrotizing.

Relatively recently, active attention has been paid to the study of the clinical features of HHV-6 infection, which can manifest itself in children sudden exanthema, otitis, diarrhea, encephalitis, hepatitis, chronic fatigue syndrome, infectious mononucleosis. Infectious mononucleosis caused by type VI HHV has a similar clinical picture to EBV- and CMV-induced mononucleosis. However, the fever is short-lived, with a moderately severe intoxication syndrome. Tonsillitis is detected in all patients, but only in 50% of cases with overlays. Lymphadenopathy in the form of multiple small lymph nodes of all groups is determined in almost all cases. Half of the children have an enlarged liver and spleen, and in every third case exanthema is detected.

Infection caused by HSV-1 and HSV-2 is characterized by pronounced clinical polymorphism. Viruses affect the central and peripheral nervous system, skin and mucous membranes, eyes, and organs of the genitourinary system. When the process generalizes, dysfunction of the liver and kidneys occurs, and a carcinogenic effect may occur (cervical cancer). Most often, herpetic lesions of the oral mucosa in children develop during primary infection and occur in the form of stomatitis. In some cases, herpetic lesions of the mucous membrane of the oropharynx occur independently or combined with stomatitis - herpetic pharyngitis, manifested by fever, intoxication, sore throat, and enlargement of the upper anterior cervical lymph nodes. Manifestations of herpetic infection are lymphadenopathy, intoxication syndrome, jaundice, hepatomegaly, splenomegaly, hepatitis, meningoencephalitis, exanthema (in 35%). Despite common clinical manifestations with EBV and CMV infections, the structure etiological factors infectious mononucleosis HSV types I, II are considered extremely rarely.

The share of infectious mononucleosis in the structure of infectious pathology has increased significantly in recent years due to a decrease in the incidence of other infections. The danger of the spread of AIDS, in which a mononucleosis-like syndrome develops several weeks or months after infection, forces us to be especially careful about each case of this infection.
Infectious mononucleosis (Filatov's disease) is an acute viral infection characterized by fever, inflammatory phenomena in the pharynx, enlarged cervical lymph nodes, spleen and liver, hematological changes and increased titer of heterophilic antibodies. This disease was first described by N.F. Filatov in 18895 under the name “idiopathic inflammation of the cervical glands.” In 1920, Sprint and Evans, having discovered hematological changes, named this disease infectious mononucleosis. In 1932, Paul and Bunnell used the heterohemagglutination test for serological diagnosis.
In the countries of Latin America, Central Africa, South Asia, the infection rate of children in the first 4 years of life is 80-90%, while in the USA, Australia, Western Europe the same percentage is registered in the group of preschool and younger children. In the European part of the USSR, the highest titers of antibodies to the causative agent of this disease are determined in preschool children.
Most researchers believe that the causative agent of mononucleosis is the Epstein-Barr virus, although it has not been isolated directly from patients. This is a DNA virus from the herpes group, spherical in shape, with 4 antigens. It is sensitive to the effects of ether. It multiplies only in cultures of Burkitt's tumor lymphoblasts, in the blood of patients with infectious mononucleosis, leukemic cells and in cultured brain cells of a healthy person. Its ability to cause lymphoid neoplasia in marmosets (a species of monkey) and owl monkeys has been established. Epstein-Barr virus has a tropism for lymphoid tissue and can persist for a long time in the host cells in the form of a latent infection. Plays an etiological role in Burkitt's lymphoma and possibly in nasopharyngeal carcinoma. The entrance gates of infection are the mucous membrane of the nose and oropharynx and the area of the pharyngeal lymphatic ring. From here, at the end of the incubation period, the virus spreads hematogenously and lymphogenously throughout the body. Settling in the lymphoid tissue, it causes in it hyperplastic processes with the formation of lymphocytic infiltrates and the release of so-called atypical mononuclear cells into the peripheral bloodstream. Despite the absence of a direct damaging effect of viruses on organ cells, functional disorders liver, kidney, nervous, cardiovascular and other systems are possible. This is due to the formation of perivascular infiltrates, accumulation of immune complexes, increased vascular permeability, which entails metabolic disorders, lymph and blood circulation in organs.
Specific cytological changes and a decrease in local immunological reactivity of the tonsils contribute to the addition of a bacterial infection with the development of inflammation. The duration of the incubation period is on average 5-20 days. The disease often begins acutely, with high temperatures, weakness, and headache. It is much less common to distinguish a prodromal period. Fever with 37.5°C is observed at the beginning of the disease and by the end of the 1st week reaches a maximum (38.5 - 40°C), then persists for several more days (up to 10-14). The temperature curve is of an irregular type, with a tendency towards a lytic decrease at the end of the febrile period. In adult patients, the temperature is higher and takes longer to reach than in children; chills are often observed at the onset of the disease. In children under 1 year of age, low-grade fever is more common. During the period of maximum temperature rise at the height of the disease, some patients may have a petechial rash on the skin and mucous membranes, nosebleeds and other bleeding, which is associated with increased vascular permeability and thrombocytopenia. In children, from the first days of the disease, damage to the nasopharynx comes to the fore, which is manifested by difficulty in nasal breathing. The child breathes with a half-open mouth, his voice takes on a nasal tone, and his face has an “adenoid” appearance. Nasal discharge is minor. Children especially suffer in the first years of life, when significant difficulty in nasal breathing and obstruction of the respiratory tract by sharply increased lymphoid tissue lead to the development of false croup syndrome with respiratory failure. In all patients, upon examination of the oropharynx, hyperemia of the pharynx and posterior wall of the pharynx with a large amount of mucus is determined, often granulosa pharyngitis (bright, coarsely expressed granularity of the posterior wall). Swelling and looseness of the tonsils - persistent symptoms diseases. Overlays on the tonsils in the form of islands, films, whitish-yellow or dirty gray stripes are not always found. They are loose, lumpy, easily removed and rubbed between glass slides. Having appeared in the first 2 days, the symptom complex of tonsillitis lasts on average 7-13 days, and in children with necrotic changes in the tonsils - even longer. In adult patients, the timing of the onset of angina is usually shifted to days 3-6 of the disease. It practically never happens in older people. On the 2-3rd day of illness, one of the main clinical symptoms of infectious mononucleosis can be detected - an increase in varying degrees of all groups of lymph nodes. The lymph nodes of the posterior cervical group enlarge to the greatest extent, forming a chain along the posterior edge of the sternocleidomastoid muscle and clearly visible to the eye. The lymph nodes become dense, retain elasticity, are not fused to each other or to the surrounding tissue, and are slightly sensitive to palpation. In younger children, the lymph nodes of the anterior cervical group often become significantly enlarged, due to which the configuration of the neck changes. Enlargement of the postmortem and lymph nodes of the abdominal cavity can cause the development of abdominal syndrome with abdominal pain, bloating, nausea, vomiting, and loose stools. The size of the lymph nodes varies from 0.5 to 3-4 cm in diameter; their reduction usually begins after 7-10 days and can last for several weeks. The enlargement of the spleen usually parallels the enlargement of the liver and reaches a maximum by the 7-10th day of the disease. On palpation, the spleen is smooth, elastic, protruding 2-4 cm from under the edge of the costal arch. There have been cases of significant enlargement of the spleen with rupture of the organ, which is one of the specific complications of infectious mononucleosis and requires immediate surgical intervention. Normalization of the size of the spleen usually occurs by the end of the 3-4th week, less often it is delayed for several months. In most cases, the enlargement of the liver is significant - its edge is dense, a slightly painful edge is palpated 3-5 cm below the costal arch. The severity of hepatomegaly (liver enlargement) is greatest in preschool children. A decrease in the size of the organ occurs only by the middle of the 2nd month of the disease. Sometimes hepatolienal syndrome persists for 6-8 months after infectious mononucleosis. In some cases, at the height of the clinical picture, the disease is accompanied by jaundice - icterus (yellowness) of the skin and sclera, sometimes a change in the color of urine and feces. Hyperbilirubinemia (increased bilirubin content in the blood serum) is usually insignificant; the enzymatic and protein synthetic functions of the liver are more impaired, as evidenced by increased performance thymol test, hypergammaglobulinemia (increased levels of serum gamma globulins), increased activity of various enzymes. Changes in the peripheral blood picture are most often detected already in the 1st week. In patients, the number of mononuclear elements of white blood (lymphocytes, monocytes, plasma cells) increases to 60-70%, which is especially often detected when calculating their absolute number. Leukocytosis reaches 20-30*109/l, ESR - 15-30 mm/hour, the number of atypical mononuclear cells increases. The diagnostic level is considered to be their content in peripheral blood above 10%. Such blood changes can last up to 2-3 months. In middle-aged and elderly patients, the blood reaction occurs later and lasts longer (up to 1-3 years), while normal ESR and leukopenia are more often observed. Rare symptoms of infectious mononucleosis include a polymorphic, esudative rash all over the body without a specific localization (maculopapular, pinpoint, roseolous, urticarial). More often, rashes occur in young children on the 2-3rd day of the disease, persist for 4-7 days and disappear, leaving no pigmentation or peeling behind. Due to damage to the lymphoid tissue of the nasopharynx and pharynx and the development of lymphostasis in children, puffiness of the face and pasty eyelids are often noticeable. Despite the usually benign course of the disease, in rare cases symptoms of kidney damage are observed in the form of interstitial nephritis. This disease often affects the nervous system with the development of meningitis, encephalitis or polyradiculoneuritis. TO specific complications infectious mononucleosis includes acute hemolytic anemia, hemorrhagic syndrome, lesion thyroid gland.
When classifying clinical forms based on the pathogenetic principle, typical and atypical forms of infectious mononucleosis are distinguished: mild, moderate and severe with complicated and uncomplicated course. Typical forms include those in which the main symptoms are clearly identified: fever, enlarged lymph nodes, changes in the oropharynx and nasopharynx, hepatolienal syndrome and characteristic hematological changes. An indicator of severity is the severity of general intoxication and the main symptoms of the disease. Atypical forms of infectious mononucleosis include erased, asymptomatic and forms with rare manifestations of the disease (i.e. with damage to the nervous, cardiovascular systems, kidneys and other organs). Erased forms are revealed during a thorough examination with the definition of weak pronounced signs diseases, serological and hematological changes, asymptomatic forms - only on the basis of epidemiological, serological and hematological data. Laboratory diagnosis is important. For earlier detection and reliable counting of atypical mononuclear cells in peripheral blood, in addition to conventional smears, the microleukoconcentration method is used, followed by staining of a leukocyte suspension.
Serological diagnosis is based on the detection of heterophilic antibodies in the patient’s serum. Paul-Bundell-Davidson agglutination reaction with sheep erythrocytes pre-treated with kidney extract guinea pig, highly specific. The diagnosis can be made at the end of the 1st, beginning of the 2nd week. The simplicity of the technique, quick results, high specificity of the Tomczyk reaction (agglutination of trypsinized bovine erythrocytes from the patient’s serum) allow us to recommend it for wide application. This reaction gives high titers (1:192), is more often positive in children under 3 years of age, and is also determined by the end of the 1st week. As an express diagnostic method, the Hoff and Bauer reaction is used - agglutination on glass of native or preserved horse erythrocytes with the patient's serum. It is convenient and easy to perform not only in hospitals, but also in clinics. A cytological examination of fingerprint smears from the surface of the tonsils reveals cells similar to atypical blood mononuclear cells. The severity of the process can be judged by the increase in the titer of immunoglobulin M. To exclude acute respiratory disease or establish a mixed infection, it is necessary to include virological reactions in the examination complex. This is especially true for young children, since the clinical picture of an acute respiratory disease against the background of their anatomical and physiological characteristics (some enlargement of the liver and spleen, damage to lymphoid tissue) may be similar to infectious mononucleosis. In addition to acute respiratory disease, mononucleosis must be differentiated from diphtheria, tonsillitis, infectious hepatitis, typhoid fever, tularemia, acute and chronic leukemia, lymphogranulomatosis, benign lymphoreticulosis, HIV infection. Diphtheritic lesions of the pharynx are accompanied by a rapid (over 1-2 days) increase in temperature, enlarged tonsils with widespread grayish-white, smooth, shiny, difficult to remove plaque, and enlarged regional lymph nodes; edema affects not only the tissues, but also spreads to the chest to the collarbones and below. Biochemical changes in the blood are pronounced and last a long time. The basis of diagnosis in doubtful cases are hematological and serological studies. In the first 4-5 days, the picture of Filatov’s disease may resemble typhoid fever, especially in middle-aged and elderly patients. However, the nature of the temperature curve, pronounced symptoms of intoxication with damage to the cardiovascular system (relative bradycardia, decreased blood pressure, roseola rash, signs of intestinal damage) make it possible to exclude infectious mononucleosis. With tularemia, lymphadenitis is detected only in the area of the entrance gate of infection (bubonic or anginal-bubonic form). Only one tonsil is affected, and lymphadenopathy can also be unilateral. The painless nodes are subsequently opened, releasing creamy pus. The skin allergy test with tularemia becomes positive from the 5th-7th day of illness. in cases of high leukocytosis (30-60*109/l) with lymphocytosis (up to 80-90%), there is a need to differentiate infectious mononucleosis from acute leukemia. The peripheral blood picture and myelogram have specific changes. In infectious mononucleosis, the presence of natural killer cells (NHL cells) among atypical mononuclear cells is an indicator of the benign nature of the process. Chronic leukemia does not have an acute onset, occurs against the background of uniform lymphadenopathy, the liver and spleen are enlarged, dense, and painless. Lymphogranulomatosis is mainly distinguished from infectious mononucleosis by the duration of the disease (months), the wavy nature of the temperature curve, the absence of damage to the pharynx and nasopharynx, the density of the lymph nodes, and neutrophilic leukocytosis. The presence of Berezovsky-Steinberg cells in lymph node punctates confirms this diagnosis. At benign lymphoreticulosis(diseases) cat scratch") in contrast to infectious mononucleosis, there is an isolated increase in the lymph nodes regional to the entrance gate of the infection, there is no sore throat, nasopharyngitis and enlargement of the posterior cervical lymph nodes.
Infectious mononucleosis can occur among people of all ages. However, children aged 3 to 10 years are predominantly affected (according to various sources, from 39 to 73%). The incidence of mononucleosis in adolescents and young adults can also be high.
Infectious mononucleosis is an anthroponotic infection. Its source is a sick person or a virus carrier. After the disease has been transmitted, in some cases the virus is periodically released for 2-5 months. Especially in large quantities The pathogen is isolated from persons undergoing immunosuppressant therapy. One should keep in mind cases of infection of medical personnel of infectious diseases hospitals with this disease. The often low incidence is apparently associated with a large percentage of immune individuals and the presence of erased and asymptomatic forms of the disease. The main route of transmission of the disease is airborne droplets. The transfusion route of transmission is also recognized.
After suffering from the disease, a person develops a strong immunity. Infants have innate maternal immunity, which explains the rarity of cases of infectious mononucleosis in this age group. In people over 50 years of age, immunity declines.
basis symptomatic therapy infectious mononucleosis is compliance bed rest until clinical symptoms disappear, complete, gentle nutrition, drinking plenty of fluids. It is necessary to provide oral care and symptomatic treatment of lesions of the oropharynx and nasopharynx. Recently, specific agents have been used in treatment: amorphous pancreatic RNase (0.5 mg/kg/day intramuscularly for 1-2 administrations for 10-14 days) and amorphous DNase (1.5 mg/kg/day intramuscularly for 7 days). A particularly noticeable positive effect in combination with courses of desensitizing therapy was obtained in severe forms with damage to the nervous system.
Prescription of antibiotics (most often penicillin series) is justified for young children with a high risk of bacterial complications, older children and adults - with developed complications. Levomycetin and sulfonamide drugs that suppress hematopoiesis are contraindicated. Experience has shown that the use of ampicillin often causes a gross exudative rash and worsens the course of the disease. In severe cases, especially with pronounced local symptoms from the nasopharynx, it is advisable to use glucocorticoids in a short course. Preventive measures consist of isolating patients in a hospital setting. Hospitalization of such patients in a general somatic hospital is unacceptable. Disinfection is not carried out in the outbreak. Persons who have contact should be observed for at least 2 weeks, especially for children and contacts in closed groups. Where possible, blood testing of contacts using serological tests can be recommended in outbreaks.

The virus was isolated only in 1964 by Epstain and Vagg from Burkitt's lymphoma cells. In honor of its discoverers, it received its name Epstain-Barr virus (EBV). In patients with Burkitt's lymphoma, high titers of antibodies to EBV were also detected. This virus, as well as high titers of antibodies to it, were detected with great consistency in infectious mononucleosis.

Infectious mononucleosis can be classified as a relatively “new” infectious diseases XX century Its study continues.

The relevance of the problem of mononucleosis is associated primarily with the widespread spread of the disease and the high degree of infection of the population by the virus, especially in developing countries, where the infection rate of children under 3 years of age reaches 80%.

The ability of the virus to persist for life, its association with slow infections, as well as with neoplastic diseases (Burkitt's lymphoma, nasopharyngeal carcinoma) have been revealed.

In addition, as it turned out in recent years, EBV acts as a marker of opportunistic infection in AIDS. This fact has given new impetus to the study of the properties of EBV and its relationship with the human immunodeficiency virus.

It has become known that EBV is detected in almost 50% of kidney transplant recipients. The cause of this phenomenon and its influence on the outcome of the operation require clarification and study.

Donated blood may pose a certain risk, since EBV can be transmitted this way. Therefore, EBV is an important problem for transfusiology.

The difficulty of studying this widespread disease lies in the fact that an experimental animal model has not yet been found in which the variants of the course and consequences of infectious mononucleosis could be studied.

Causes of mononucleosis

EBV belongs to the herpesvirus group. The size of the virus is 180-200 nm. It contains double-stranded DNA and has 4 main antigens:

Early antigen (early antigen - EA), which appears in the nucleus and cytoplasm, preceding the synthesis of viral particles, contains D- and R-components;

Capsid antigen (viral capcide antigen - VCA), contained in the nucleocapsid of the virus; in infected cells containing the EBV genome but lacking VCA in the cytoplasm, virus replication does not occur;

Membrane antigen (MA);

Nuclear antigen (Epstain-Barr Nuclea antigen - EBNA), consisting of a complex of polypeptides.

There are A and B strains of EBV. They are found in different geographical areas, but significant differences between the strains themselves and in the nature and course of the pathological conditions caused by them have not yet been identified.

EBV shares antigens with herpes simplex virus.

The virus is tropic for B-lymphocytes that have surface receptors for it. They contain either the synthesis of complete particles of the virus, or only its individual components (antigens). Unlike other herpesviruses, EBV does not destroy the cells in which it multiplies. It can only be cultivated in human and primate cell cultures (B-lymphocytes).

EBV is capable of long-term persistence in the human body in B lymphocytes (the main target cells). But research in recent years has proven the presence of the virus in the epithelial cells of the oropharynx and nasopharynx.

Epidemiology

The only source of infection is a person (patient or virus carrier). EBV can be excreted in saliva up to 12-18 months after clinical recovery. Moreover, the ability of the virus to persist in the body for a long time, sometimes for life, can cause another “burst” of virus release against the background of diseases accompanied by immunosuppression.

The entry gate for the virus is the mucous membrane of the nasopharynx. The disease is not highly contagious and occurs only in close contact with a patient, when droplets of saliva containing the virus fall on the mucous membrane of the nasopharynx. It is most easy to become infected through airborne droplets (coughing, sneezing) or through kissing; this is what led to the peculiar name of this disease “lovers’ disease”, “disease of brides and grooms”. You can also become infected through infected household items (cups, spoons, toys). The possibility of transfusion and sexual transmission is possible.

People of any age can get sick. Most often, mononucleosis affects children aged 2-10 years. The next increase in incidence is observed among people aged 20-30 years. Children under 2 years of age rarely get sick; the disease they develop is often subclinical. 20-30 years is the “age of love”; this, perhaps, can explain the next rise in incidence. By the age of 40, most people are infected, which is detected serological reactions. In developing countries, by the age of 3 years, almost all children are infected.

Typically, the incidence is sporadic, recorded in the form of familial outbreaks. But epidemic outbreaks are possible in closed groups (kindergartens, military schools, etc.). The peak incidence usually occurs during the cold season.

Diseases caused by strain A are widespread; in the European region they occur mainly in the form of clinically pronounced or inapparent forms of infectious mononucleosis. Strain B is found mainly in Asia and Africa, where nasopharyngeal carcinoma (China) and Burkitt's lymphoma (African countries) are recorded, but in these regions the incidence of infectious mononucleosis is much higher than in developed countries.

Classification of mononucleosis

There are many classifications of infectious mononucleosis, but none of them is generally accepted due to its cumbersomeness and imperfection.

You should adhere to the simplest classification of infectious mononucleosis.

1. Manifest forms, which can be characterized by mild, moderate and severe course. Manifest forms occur typically or atypically (erased, visceral).

2. Subclinical forms (they are usually diagnosed by chance or during a targeted examination of contacts).

Infectious mononucleosis can occur as acute, prolonged or chronic infection. Based on clinical manifestations and even immunological studies in newly diagnosed mononucleosis, it can be difficult to judge whether this is a fresh infection or an exacerbation of a latent infection. Therefore, when formulating a diagnosis, the term “acute” is usually omitted. Recurrent disease if the first case is documented, it can be regarded as a relapse.

Approximate formulation of the diagnosis. 1. Infectious mononucleosis, mild course. 2. Infectious mononucleosis (relapse), moderate course.

Due to the lack of an experimental model, the pathogenesis of mononucleosis has not been sufficiently studied; many provisions are hypothetical and require detailed study and confirmation. The pathogen enters through the mucous membrane of the nasopharynx into the pharyngeal lymph nodes, where B lymphocytes are present. Due to the presence of specific receptors on the surface of B lymphocytes, EBV attaches to the cell and invades it, and EBNA penetrates into the nucleus of the infected lymphocyte. Viral synthesis begins with the replication of multiple copies of the viral genome. Infected cells, when multiplying, receive their share of EBV gene copies in latent form. The virus is assembled in the cytoplasm, and only in the presence of all components, primarily VCA, is a full-fledged virus formed, which in turn is capable of producing offspring. Increasing the number of infected cells containing viruses, capable of reproduction and incapable (i.e. without VCA), the accumulation of virus is a relatively slow process. In addition, EBV has another property - it can integrate into the gene of an infected cell (integrative pathway). Histological examination of biopsies taken from patients with infectious mononucleosis, nasopharyngeal carcinoma, and Burkitt's lymphoma can simultaneously detect various options damage to lymphocytes. Regardless of which way the relationship between the virus and the host cell takes place, the affected cell does not die.

As the virus multiplies and accumulates, it penetrates the regional lymph nodes, and 30-50 days after infection enters the blood, where it infects blood B-lymphocytes and penetrates all organs containing lymphoid tissue. Thus, the generalization of the process and dissemination of the virus occurs.

In the lymphocytes of the affected organs and tissues, in the blood lymphocytes, a process similar to that which took place in the nasopharynx during the initial infection occurs.

What causes the development of the disease? Immune mechanisms are believed to play a major role. Already at the stage of virus replication and accumulation in the oropharynx, EBV actively stimulates the production of IgM, IgA, and IgG. In infectious mononucleosis, the variety of antibodies produced is striking, the role of most of them in pathogenesis has not yet been studied. Thus, along with specific antibodies directed against the virus and its individual fragments, heterophilic antibodies appear, which, as revealed, cause hemolysis of bovine erythrocytes and agglutination of sheep and horse erythrocytes. Their role is all the more unclear because there is no correlation between the severity of the disease and titers of heterophilic antibodies. Antibodies are also detected against one’s own neutrophils, lymphocytes, ampicillin (even if it was not used as a therapeutic drug), and to various tissues. This undoubtedly affects the course of the disease and acquires special significance, contributing to the occurrence of various complications.

The T-cell immune response also plays a significant role. In the acute stage of the disease, T-lymphocytes are stimulated, as a result of which T-killers and T-suppressors strive to suppress the proliferation of B-lymphocytes, T-killers lyse cells infected with EBV, which leads to a gradual release from the pathogen. At the same time, the presence of various isoantigens promotes the participation of T lymphocytes in the implementation of the “host versus graft” type reaction.

After the disease, antibodies against capsid (VCA) and nuclear (EBNA) antigens can persist throughout life, most likely due to the persistence of EBV in the body. Thus, clinical recovery does not coincide in time with cleansing the body of the virus.

The presence of antibodies to capsid antigen (CA) protects the body from possible EBV superinfection. This may play a very important role, since, as it turned out in an in vitro experiment, B lymphocytes infected with EBV acquire the ability to endlessly divide. This property of “immortality” is revealed only by lymphocytes obtained from people who have previously suffered from infectious mononucleosis. Doesn't this contribute to the emergence malignant forms in vivo?

The subclinical course of the disease is not accompanied by pronounced immune changes, but it can also develop into latent form. In immunosuppressive conditions, infection may become activated with pronounced clinical manifestations. Clinical exacerbation under the influence of immunosuppressive therapy can occur in persons who suffered from infectious mononucleosis many years ago.

The pathogenesis of malignant forms - nasopharyngeal carcinoma and Burkitt's lymphoma - has not been studied. Perhaps the ability of viral DNA to integrate into the DNA of the host cell, the ability of cells to “immortality” during EBV superinfection, and the conditions for such superinfection that exist in developing countries are part of the factors responsible for this unfavorable process.

Moreover, it is increasingly possible to detect antibodies to EBV in patients with lymphogranulomatosis, sarcoidosis, and systemic lupus erythematosus, which still requires explanation.

Infectious mononucleosis is an HIV-associated disease. Considering the high degree of infection of the population around the globe, we can talk about an exacerbation of latent infection against the background of immunodeficiency, which is natural for HIV infection.

The lack of clear knowledge so far about the features of the pathogenesis of infectious mononucleosis allows us to speak only with a certain degree of certainty about the pathogenesis of some of the most constant symptoms.

Clinical course of mononucleosis

The incubation period of mononucleosis ranges from 20-50 days. Usually the disease begins with prodromal symptoms: weakness, myalgia, headache, chills, loss of appetite, and nausea. This condition can last from several days to 2 weeks. Subsequently, a sore throat and a temperature that reaches 38-39 °C arise and gradually increase. By this time, most patients exhibit a clinical triad of symptoms that are considered classic for infectious mononucleosis - fever, lymphadenopathy, sore throat.

Fever is a very constant symptom. It is observed in 85-90% of patients, although cases occurring with low-grade and even normal temperature are possible. Chills and sweat are not typical. The nature of the temperature curve is very different - constant, remitting, duration - from several days to 1 month or more. Usually there is no clear correlation between the nature of the temperature curve and the severity of other clinical symptoms.

Lymphadenopathy is one of the most typical and early signs of infectious mononucleosis; it disappears later than others pathological manifestations. The first to enlarge are the cervical lymph nodes, located in the form of a garland along the m.sternoclei-domastoideus. Already at the height of the disease, in most patients it is possible to detect an increase in other groups of lymph nodes - peripheral (axillary, inguinal), internal (mesenteric, peribronchial). Enlargement of internal lymph nodes can cause the appearance of additional clinical symptoms - abdominal pain, cough and even difficulty breathing. Abdominal pain localized in the right iliac region may simulate acute appendicitis, especially in children.

Enlarged lymph nodes can range from the size of a pea to a walnut. They are not fused to each other and to the underlying tissues, are moderately painful, are not prone to suppuration, and the skin over them is not changed.

Sore throat is caused by local inflammatory changes. The mucous membrane of the posterior wall of the pharynx is hyperemic, edematous, hypertrophied follicles are visible (granular pharyngitis). The tonsils are enlarged, loose, and often have a delicate whitish coating on them, caused by local exudation. Activation of a secondary infection (usually streptococcal) is also possible; in this case, dirty gray plaques appear on the tonsils, easily removed, and festering follicles are visible. Due to the enlargement of the adenoids, the voice may acquire a nasal tone.

A common symptom of infectious mononucleosis is hepato-splenomegaly.

Liver enlargement can be detected by palpation in 50-60% of patients, and by ultrasound in 85-90%. In this case, there is always a moderate (several times) increase in the activity of cytolytic enzymes, and in a small part of patients a slight jaundice is detected, sometimes noticeable only on the sclera. As the liver recovers, it gradually shrinks, but sometimes it remains enlarged for several weeks; enzymatic parameters return to normal earlier. The spleen is just as often enlarged, but it is not always possible to palpate it. The enlarged spleen is dense, elastic, painless on palpation; its significant increase causes a feeling of heaviness and discomfort in the left hypochondrium. In rare cases, it may become so significantly enlarged that deep or rough palpation can lead to its rupture. Every doctor who begins a manual examination of a patient should remember this. Hepatolienal syndrome is usually most pronounced by the 5-10th day of illness.

In 10-15% of patients, rashes appear on the skin and mucous membranes. The rash can be very different - urticarial, macular, hemorrhagic, scarlet-like. The timing of its appearance is very different. Enanthema may appear on the soft palate.

The duration of the disease is usually at least 2-4 weeks. The first 2 weeks correspond to the height of the disease, during which time the temperature and symptoms of general intoxication (weakness, nausea, headache, myalgia, arthralgia) persist. Complications characteristic of infectious mononucleosis (see below) usually develop in the 2-3rd week, at about the same time the period of convalescence begins: body temperature decreases, intoxication symptoms decrease, lymph nodes, liver, spleen become smaller, the hemogram gradually normalizes. But the process can drag on for 2-3 months or even longer, in which case it is regarded as protracted.

In children under 2 years of age, the disease is often asymptomatic. The younger the child, the less clearly the picture of infectious mononucleosis emerges. In adults, the ratio of clinically pronounced and asymptomatic forms is 1:3 and even 1:10.

Atypical forms of infectious mononucleosis are characterized by the absence of any leading symptom of the disease (fever, hepatosplenomegaly, lymphadenopathy, tonsillitis) or unusual severity of any symptoms (severe generalized lymphadenopathy, significant enlargement of the lymph nodes of only one localization, severe jaundice, etc. .).

When the course is erased, the clinical manifestations are not clear enough, and it is they that determine greatest number diagnostic errors (especially in cases where the patient has not even had a general blood test done).

The severity criteria are the severity of the general intoxication syndrome, the duration of the disease, the presence and nature of complications.

We can speak of a protracted course of infectious mononucleosis if hematological changes and lymphadenopathy persist for up to 6 months.

Chronic forms of infectious mononucleosis are just beginning to be studied. Long-term persistence of EBV may be due to immunodeficiency, including HIV infection. In addition, we should not forget about the ability of EBV to induce the development of neoplastic processes and autoimmune diseases. Therefore, in all cases when a patient has long-term (6 months or more) after suffering from infectious mononucleosis, residual effects persist in the form of pronounced asthenovegetative syndrome, dyspeptic symptoms, low-grade fever, etc., even in the absence of clear lymphadenopathy and hepatosplenomegaly, he must be subjected to an in-depth examination for the presence of EBV markers, and sometimes perform histological studies of bone marrow punctures, lymph nodes, and liver. Only in this case will it be possible to say with a certain degree of probability whether the patient has chronic mononucleosis or its consequences, which determined the development of a qualitatively new pathological condition. Considering the ability of EBV to act as an immunosuppressant, we should not forget about the possibility of developing mixed pathology against the background of persistent EBV. In these cases, it is necessary to clarify the relationship of individual clinical manifestations with each of the etiological factors of mixed pathology.

Complications

Uncomplicated infectious mononucleosis has a relatively benign course and is almost fatal.

However, when complications occur, which are quite rare, the prognosis worsens significantly. The nervous system, heart muscle, liver, spleen are most often affected, and of various nature hematological disorders. In most cases, they are based on autoimmune reactions, the action of immune complexes, intoxication, and the direct influence of the virus. Many reasons are not yet well understood.

Neurological complications, usually occurring in the form of aseptic meningitis, encephalitis, meningoencephalitis, are more common in children and young people.

Meningitis develops during the acute period of the disease (end of the 1st-2nd week of illness). Patients complain of persistent headache, nausea, vomiting that does not bring relief, convulsions, loss of consciousness, and meningeal signs may occur. The clinical picture of meningitis can be so bright that the clinical manifestations of infectious mononucleosis itself fade into the background; they are not given much importance until a characteristic blood test is obtained. When researching cerebrospinal fluid Lymphocytic pleocytosis (moderate) is detected, sometimes with the presence of mononuclear cells; sugar and protein are usually normal. The duration of such meningitis ranges from several days to several weeks. Lethal outcomes are possible, but more often the process ends in complete recovery.

Much great danger represents encephalitis that occurs against the background of infectious mononucleosis. The localization of the process can be very different (cortex, cerebellum, medulla oblongata), which causes a large polymorphism of clinical symptoms (chore-like movements, paralysis, damage to the respiratory center with breathing problems, comatose states). The phenomena of encephalitis can be combined with damage to the spinal cord, peripheral and cranial nerves, which increases the range of clinical manifestations. Sometimes such patients develop mental disorders (psychomotor agitation, hallucinations, deep depression, etc.). The prognosis is determined by the localization, prevalence of the process, timeliness of its recognition and treatment. But it is encephalitis that poses the greatest danger to the patient’s life, since it can progress rapidly. In this case, if the process can be dealt with quickly, there are usually no residual effects.

With primary infection, other lesions of the nervous system are possible, such as Guillain-Barré syndrome (ascending acute polyradiculoneuritis with protein-cell dissociation in the cerebrospinal fluid), Bell's palsy (paralysis of facial muscles caused by damage to the facial nerve), and transverse myelitis.

Hematological complications arising from infectious mononucleosis are mainly caused by autoimmune reactions. In rare cases, the disease may be accompanied by leukopenia, severe agranulocytic reaction, and thrombocytopenia. Significant thrombocytopenia may be accompanied by bleeding, thrombocytopenic purpura, and antibodies against platelets are detected in the blood. Hemorrhagic syndrome sometimes accompanied by retinal hemorrhage. Severe autoimmune anemia may develop.

A serious complication, in most cases leading to the death of the patient, is rupture of the spleen, which in patients with infectious mononucleosis can increase several times. The cause of the rupture may be a sudden movement of the patient or rough palpation. Usually this complication occurs in the 2-3rd week of illness, and sometimes it can be the first manifestation of the disease.

Liver enlargement is one of the most persistent manifestations of infectious mononucleosis. But in some patients it is accompanied by jaundice (mild or significant) and a distinct increase in the activity of cytolytic enzymes, which can be classified as hepatitis.

Often, with infectious mononucleosis, a slight dullness of heart sounds is detected, and moderate tachycardia appears. But some patients may experience myocarditis and pericarditis, which is confirmed by ECG studies.

The course of the disease, especially in children, can be complicated sudden swelling tonsils and pharyngeal mucosa, which is accompanied by the development of airway obstruction. The cause of obstruction (more often in young children) can also be enlargement of the paratracheal lymph nodes; in these cases, even surgical intervention may be required.

During the period of convalescence, the development of interstitial nephritis of autoimmune origin is possible. A more rare complication is damage endocrine glands with the development of mumps, orchitis, pancreatitis, thyroiditis.

The course of infectious mononucleosis can be complicated by the addition of an exogenous or activation of an endogenous infection.

Outcomes. In 90-95% of patients, in the absence of complications, the disease ends in recovery. The presence of complications (especially hematological and those associated with damage to the central nervous system) sharply worsens the prognosis.

Of particular interest is the ability of the virus to persist for a long time after clinical recovery. The role of EBV persistence is not well understood.

The action of EBV as an oncogene has been convincingly proven. In patients with Burkitt's lymphoma and nasopharyngeal carcinoma, the EBV genome is detected in biopsies, and high titers of antibodies to this virus are found in the blood. EBNA is consistently detected in the nucleus of Burkitt's lymphoma cells on biopsy. Perhaps, in the peculiarities of the interaction of the virus with the body, given the limited spread of these diseases, ethnic and genetic factors play a significant role. This is supported by data on the connection between some variants severe course infectious mononucleosis with the X chromosome (Duncan syndrome), with severe hematological and autoimmune complications and lymphocytic lymphoma more often occurring. EBV is also found in several other malignant diseases that are ubiquitous.

In recent years, the so-called “chronic fatigue syndrome” has attracted the attention of clinicians, in which antibodies to EBV are often detected in the blood. However, given the widespread prevalence of infectious mononucleosis and the possibility of long-term persistence of the pathogen in the body, a convincing connection between this syndrome and EBV infection has not yet been proven.