Prevention of rheumatic fever: modernity and a look into the future

Prevention of rheumatism

Prevention of rheumatism can be primary and secondary. Primary prevention involves a set of measures that are aimed at reducing the chances of streptococcal infections, and if it occurs, timely and competent treatment.

Prevention of rheumatism: characteristic points of primary and secondary prevention

• Primary prevention is characterized by maintaining an active and healthy lifestyle, walking in fresh air, ventilating rooms, hardening the body and a balanced diet.
• It is worth noting that isolating a person who has contracted a streptococcal infection, as well as monitoring people who were previously in contact with him, is a mandatory measure.
• Primary prevention also includes the sanitation of foci of infection, in particular in the nasopharynx (sinusitis, pharyngitis, sinusitis). Sanitation of the nasopharynx is especially recommended for children, adolescents and young people suffering from constant exacerbations of nasopharyngeal infections. In this case, the rehabilitation should be radical, but the methods of treating the disease rheumatism themselves are determined by a specialist doctor.
• It is extremely important to start fighting the infection on time. It is believed that timely treatment is one that is started no later than the third day from the onset of infection. It is in this case that the possibility of rheumatism is practically eliminated. Acute streptococcal infection is treated by taking antibiotics for 10 days. In parallel with taking antibiotics, anti-inflammatory drugs are usually prescribed, which are taken for at least a week.
• After suffering a streptococcal infection, the patient must undergo a thorough examination, namely: blood and urine tests, and only if the indicators are normal, discharge is allowed.

Thus, for the correct organization of primary prevention, it is important to comply with all the described measures in combination. I would like to emphasize that responsibility for the effectiveness of the treatment carried out lies not only with the doctor, but also with the patient himself, because cases of a person seeking help already at the extreme stages of the disease are extremely common. In such cases, fighting the disease is much more difficult. Therefore, the attitude of the person himself to his health plays a primary role.

Secondary prevention is a set of measures aimed at preventing relapses and progression of the disease in people who have already suffered a rheumatic attack. The peculiarity of the development of rheumatism is its tendency to recur. In accordance with this, its prevention involves a long course of measures. Dispensary observation plays a key role in this case. It is usually carried out by a rheumatologist or in specialized rheumatology centers.

Secondary prevention includes the following areas:

• ensuring strengthening of the body's resistance: general health regime, hardening, balanced nutrition, physical therapy;
• bicillin prophylaxis, which is necessary to combat streptococcal infection;
• long-term antirheumatic therapy with non-steroidal anti-inflammatory drugs;
• carrying out sanitation of chronic foci of this infection.

Bicillin prophylaxis of rheumatism

Bicillin prophylaxis is a key link in the prevention of rheumatism. It was found that the administration of bicillin for preventive purposes is indicated for all people who have suffered a rheumatic process.

For patients who have suffered polyarthritis or primary rheumatic carditis without damage to the heart valves, bicillin-drug prophylaxis should be carried out for 3 years.

For those who have suffered primary rheumatic carditis along with damage to the heart valves, as well as for patients with recurrent rheumatic carditis, prophylaxis should last at least 5 years.

In cases where, during bicillin prophylaxis, a person still gets sick with pharyngitis or tonsillitis, he is prescribed a 10-day treatment course of antibiotics along with anti-inflammatory drugs. This is called ongoing rheumatic fever prevention. If during a period of illness a person needs to undergo surgery, for example, to pull out a tooth or remove tonsils, then this must be accompanied by penicillin.

Bicillin-5 is prescribed to pregnant women who suffer from rheumatism from approximately 8-10 weeks of pregnancy.

In winter and spring, it is recommended to combine prevention through medications with taking vitamins. Ascorbic acid is a great example of this.

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Prevention of rheumatic fever: modernity and a look into the future

Chronic rheumatic heart disease (CRHD) is a disease characterized by persistent damage to the heart valves in the form of post-inflammatory marginal fibrosis of the valve leaflets or formed heart disease (failure and/or stenosis) after ARF. In the second half of the 20th century, the incidence of ARF and CRHD and the mortality caused by them decreased, and the life expectancy of patients increased. The decrease in morbidity was closely related to the implementation of socio-economic transformations, increasing living standards, and improving the quality of medical and preventive measures. However, in recent years it has become obvious that the mentioned measures, although they help reduce the incidence of ARF and CRHD, do not completely solve the problem of combating these diseases. In modern Russia, due to known negative social changes, there is a danger of true outbreaks of ARF. In particular, in 1994, compared to the previous year 1993, there was an increase in the primary incidence (detection) of ARF from 0.06 to 0.16‰ among children and from 0.08 to 0.17‰ among adolescents. This growth occurred primarily in the North Caucasus region, especially in the republics of Ingushetia and Dagestan. However, throughout the country as a whole, doctors should be constantly alert to possible outbreaks of ARF due to the non-declining rates of primary incidence (detection) of CRHD. The vast majority in this category are patients with acquired rheumatic heart disease (ARV). By the end of the last decade of the last century, 2.5 thousand more patients with CRHD were diagnosed in Russia annually than at the beginning of registration (1994). At the same time, the prevalence of CRHD increased most significantly (from 1.4 to 2.3 per 1000) due to the population of the North Caucasus, i.e. where an outbreak of ARF was reported in 1994. Consequently, the problems of ARF and CRHD should continue to be the focus of attention of medical scientists, health care managers and practitioners. According to the statistical report of the Ministry of Health and Social Development of the Russian Federation for 2006, the prevalence of CRHD remains high and amounts to 2.21 per 1000 population. At the same time, about 220 thousand patients require regular year-round secondary prevention of ARF. The program for preventing ARF and repeated attacks of the disease includes primary and secondary prevention. The main goals of primary prevention are as follows. 1. Measures aimed at increasing the level of natural immunity and adaptive capabilities of the body in relation to unfavorable environmental conditions. These include: – early hardening; – complete fortified diet; – maximum use of fresh air; – rational physical education and sports; – combating overcrowding in homes, preschool institutions, schools, colleges, universities, public institutions; – implementation of a set of sanitary and hygienic measures that reduce the possibility of streptococcal infection of groups, especially children. 2. Timely and effective treatment of acute and chronic recurrent GABHS infection of the pharynx: tonsillitis (tonsillitis) and pharyngitis. GABHS is transmitted by airborne droplets. The likelihood of infection increases with high contamination and close contact. Sources of infection are sick and (less often) asymptomatic carriers. The infection spreads quickly, especially in organized groups. Mostly children aged 5–15 years and young people are affected. Accurate official statistics on GABHS infections are not available. However, as evidenced by the results of American researchers, almost every child who has reached the age of 5 has a history of GABHS infection of the pharynx, and at the age of 13 years the number of episodes of the disease reaches three [1]. The highest incidence of GABHS tonsillitis/pharyngitis is observed in early spring. Pharyngitis caused by the influenza virus, coronaviruses, and respiratory syncytial viruses occurs mainly in the autumn and winter. The clinical picture of GABHS tonsillitis is well known and is presented in a number of publications available to Russian doctors [2–4]. In the framework of this article, I would like to emphasize once again that the diagnosis of GABHS tonsillitis must be confirmed by a microbiological examination of a smear from the surface of the tonsils and/or the posterior wall of the pharynx. However, the cultural method does not allow differentiating an active infection from a GABHS carriage, and modern rapid tests, despite their high specificity, are characterized by relatively low sensitivity, i.e. a negative result of rapid diagnosis does not exclude streptococcal etiology of the disease. Currently, Canadian authors [5] have developed and tested a clinical algorithm on a large group of patients, which makes it possible, at the first examination of a patient, to assume the presence of GABHS infection of the pharynx and, accordingly, to resolve the issue of prescribing empirical antimicrobial therapy if it is impossible to perform a microbiological study (Table 1) . It must be borne in mind that in 1/3 of cases, ARF is a consequence of GABHS-tonsillitis, which occurs with erased clinical symptoms (satisfactory general condition, body temperature is normal or subfebrile, a slight feeling of soreness in the throat, disappearing after 1-2 days), when the majority patients do not seek medical help, but carry out treatment independently without the use of appropriate antibiotics. Considering the possibility of spontaneous relief of the clinical symptoms of GABHS tonsillitis and recovery without any complications, some doctors, when supervising such patients, completely unreasonably give preference to local treatment (rinsing, inhalation, etc.) to the detriment of systemic antibiotic therapy. Such an approach seems completely wrong and even harmful for the patient due to the threat of developing very serious consequences. In connection with the above, it should be emphasized that an accurate diagnosis and mandatory rational antibiotic therapy for GABHS tonsillitis still play a crucial role both in controlling the spread of this infection and in the prevention of ARF. In 1931, A. Coburn and A. Moor were the first to use sulfonamide drugs for prophylactic purposes in patients with CRHD. This was followed by a number of reports about their positive preventive effect in small doses (in particular, 1 g of sulfadimezine per day). However, despite some positive results, the use of these drugs turned out to be ineffective due to the increase in resistant GABHS strains. In the mid-40s. last century, world clinical medicine received at its disposal the first antibiotic - penicillin G. In 1948, work by Danish authors was published, indicating the successful use of this drug for GABHS infection. However, the true significance of penicillin was established several years later in studies carried out with the participation of recruits at a US Air Force base in Wyoming. The use of a depot form of penicillin G made it possible to achieve eradication of GABHS from the pharynx in 93% of patients. Moreover, the incidence of ARF among individuals treated with penicillin decreased by 90% (!!) compared with the group that did not receive treatment [6,7]. At the end of the 1950s, an acid-resistant dosage form of the drug (penicillin V, phenoxymethylpenicillin) was introduced into clinical practice, which made it possible to carry out successful therapy for GABHS infections of the pharynx with oral administration of the antibiotic. Subsequently, the effectiveness and safety of penicillins was confirmed in numerous clinical studies involving a large number of patients (children and adults). Despite the fact that GABHS still retains almost complete sensitivity to b-lactam antibiotics, in recent years certain problems have been noted in the treatment of tonsillitis caused by this microorganism. According to various authors, the failure rate of penicillin therapy for GABHS tonsillitis is 24–30% and even reaches 38%. The following are cited as possible reasons for this phenomenon. 1. Low compliance (performance) of patients. It is known that in more than half of the patients, fever and sore throat disappear on the 4th day of illness, and at the end of the 6th day, the clinical symptoms of GABHS tonsillitis are relieved almost completely. In this regard, many patients stop taking the antibiotic on their own. According to available data, when a standard 10-day regimen of penicillin therapy was prescribed, only 8% of patients continued taking the drug on the 9th day [8]. Moreover, an analysis of the causes of the ARF outbreak in the United States in the mid-1980s. revealed that in 10–15% of cases there was non-compliance with the timing of treatment with penicillin for a GABHS infection of the pharynx that preceded the disease. 2. Hydrolysis of penicillin by specific enzymes - b-lactamases, which are produced by microorganisms - co-pathogens (S. aureus, H. influenzae, M. catarrhalis, etc.) present in the deep tissues of the tonsils during chronic tonsillitis. It is known that in healthy individuals, the tonsils are normally colonized by oropharyngeal microflora, representing about 100 different types of commensal microbes. In the presence of a chronic inflammatory process in the tonsils and under the influence of antibiotics (especially penicillin), the composition of the oral flora undergoes changes, expressed in an increase in the number of bacterial strains capable of producing b-lactamases (selective pressing phenomenon). It has been shown that by the end of the 20th century, the detection rate of co-pathogens producing b-lactamases in children with chronic recurrent tonsillitis increased to 94%. 3. Reinfection with GABHS. The risk of reinfection is especially high in closed and semi-closed groups (kindergartens, schools, colleges, day hospitals, etc.) It is reported that reinfection can develop through contact with both an infected person and contaminated objects. Among 104 children who received a 10-day course of penicillin for GABHS tonsillitis, A-streptococci were repeatedly isolated on removable orthodontic appliances (19% of cases) and on toothbrushes (11% of cases). The authors conclude that these items are likely to be a source of reinfection in some patients [8]. 4. Violation of colonization resistance. a-streptococci, which are representatives of the saprophytic microflora of the pharynx, protect the latter from GABHS colonization. It was shown that after a course of antibiotic therapy in patients whose oropharynx was colonized with a-streptococci (in the form of an oral spray), there was a lower frequency of relapses of GABHS tonsillitis than in the control group (2 and 23%, respectively) [9]. Consequently, the bactericidal effect of penicillin on a-hemolytic streptococci may disrupt this protective mechanism. 5. Carriage of GABHS. The increasing number of failures of penicillin therapy may be a reflection of the increase in the population of GABHS carriers - individuals whose oropharynx is colonized with A-streptococci, but there are no clinical symptoms of infection. The prevalence of GABHS carriage among schoolchildren in regions with temperate climates can reach 20%, while in hot countries it exceeds 40%. In one study, the frequency of GABHS carriage among healthy children was 2.5%, among children with upper respiratory tract infections of presumably viral etiology - 4.4%, among children with upper respiratory tract infections with verified viral etiology - 6.9% [10 ]. 6. The phenomenon of internalization. A number of studies have shown that GABHS, which are essentially extracellular pathogens, can penetrate into the epithelial cells of the mucous membrane of the respiratory tract and thus be protected from the action of b-lactam antibiotics [11,12]. As can be seen from Table 2, penicillin drugs remain the means of choice in the treatment of acute forms of GABHS tonsillitis. The optimal drug from the group of oral penicillins is amoxicillin, which is similar in antistreptococcal activity to ampicillin and phenoxymethylpenicillin, but significantly superior to them in its pharmacokinetic characteristics, characterized by greater bioavailability (95, 40 and 50%, respectively) and a lower degree of binding to serum proteins (17, 22 and 80% respectively). The administration of ampicillin in oral form for the treatment of GABHS tonsillitis, as well as respiratory tract infections of other localizations, is currently considered inappropriate by most authors due to the unsatisfactory pharmacokinetic characteristics of the drug (primarily low bioavailability). The use of phenoxymethylpenicillin seems justified only in younger patients, given the presence of a dosage form in the form of a suspension, as well as somewhat greater compliance, controlled by parents, which cannot be said about adolescents. Prescribing a single injection of benzathine penicillin is advisable in the following situations: – low performance of patients; – ARF and/or a history of chronic rheumatic heart disease in close relatives; – unfavorable social and living conditions (crowding factor); – outbreaks of GABHS infection in organized groups; – impossibility of oral administration. Along with penicillins, cefadroxil, a representative of the first generation oral cephalosporins, deserves undoubted attention, its high effectiveness in the treatment of A-streptococcal tonsillitis, as well as good tolerability, have been confirmed in numerous clinical studies. In case of intolerance to b-lactam antibiotics, it is advisable to prescribe macrolides (spiramycin, azithromycin, josamycin, roxithromycin, clarithromycin, midecamycin), the antistreptococcal activity of which is comparable to that of penicillin. These drugs also have the ability to create high tissue concentrations at the site of infection and are well tolerated. The use of erythromycin, the first representative of this class of antibiotics, has now significantly decreased, especially in therapeutic practice, since it most often, compared to other macrolides, causes undesirable effects on the gastrointestinal tract due to its stimulating effect on gastric and intestinal motility . It should be noted that at the end of the 20th century, reports began to be received from Japan and a number of European countries about the increasing resistance of GABHS to erythromycin and other macrolides. In modern reality, acquired resistance of GABHS to erythromycin is quite widespread, and in some European regions it exceeds 40%. The main mechanisms of resistance (methylation and active clearance) are represented in approximately equal proportions. Using the example of Finland, it was shown that this resistance is a controlled process [13]. After GABHS resistance to macrolides in this country reached 19%, health authorities took a number of administrative measures and conducted a wide educational campaign among the population. This led to a twofold decrease in the consumption of macrolides and, as a consequence, a twofold decrease in the frequency of GABHS strains resistant to the mentioned antibiotics. In Russia, GABHS resistance to macrolides ranges from 4.8 (Central region) to 14% (Ural) [14]. There are reports in the literature of the high effectiveness of 5-day courses of clarithromycin, cefuroxime, cefixime and other antibiotics in the treatment of GABHS tonsillitis in children and adults. However, the results of these studies have not yet received official recognition from regulatory organizations and, according to experts, should be confirmed in further large-scale studies with careful microbiological verification and serological typing of the isolated GABHS strains. Lincosamide antibiotics (lincomycin, clindamycin) also have high antistreptococcal activity, but they are prescribed to patients with GABHS tonsillitis only if they are intolerant to both b-lactams and macrolides. Widespread use of these drugs for this nosological form is not recommended. It is known that with frequent use of oral penicillins, sensitivity to them from viridans streptococci localized in the oral cavity is significantly reduced. Therefore, in this category of patients, among whom there are a sufficient number of patients with rheumatic heart disease, lincosamides are considered as first-line drugs for the prevention of infective endocarditis when performing various dental procedures. As already indicated, in the presence of chronic recurrent GABHS tonsillitis, the probability of colonization of the site of infection by microorganisms producing b-lactamases is quite high. In these cases, it is advisable to carry out a course of treatment with inhibitor-protected penicillins (amoxicillin/clavulanate) or second-generation oral cephalosporins (cefuroxime-axetil), and in case of intolerance to b-lactam antibiotics, with lincosamides (Table 3). These antibiotics are also considered as second-line drugs for cases of unsuccessful penicillin therapy for acute GABHS tonsillitis (which is more common when using phenoxymethylpenicillin). There is no universal scheme that ensures 100% elimination of GABHS from the nasopharynx in global clinical practice. It should be noted that the use of tetracyclines, sulfonamides, co-trimoxazole and chloramphenicol for GABHS infection of the pharynx is currently not justified due to the high frequency of resistance and, consequently, low rates of treatment effectiveness. The prescription of early fluoroquinolones (ciprofloxacin, pefloxacin, ofloxacin, lomefloxacin) is also not justified due to the low natural antistreptococcal activity of these drugs. Secondary prevention is aimed at preventing recurrent attacks and progression of the disease in people who have had ARF, and involves regular year-round administration of long-acting penicillin (benzathine benzylpenicillin). The drug is administered deeply intramuscularly to children weighing up to 27 kg at a dose of 600,000 units once every 3 weeks, children weighing > 27 kg - 1,200,000 units once every 3 weeks, adolescents and adults - 2,400,000 units once every 3 weeks. The duration of secondary prevention (which should begin in the hospital) for each patient is determined individually and, in accordance with WHO recommendations, is determined by the presence of risk factors for repeated attacks of ARF. These factors include: • Age of the patient • The presence of HRBS • The time from the moment of the first attack of the eagle • The number of previous attacks • The factor of crowding in the family • Family history, weighed down by ORL/HRBS • Socio -economic and educational status of the patient • The risk of streptococcal infection in the region • The profession and place of work of the patient (school teachers, doctors, persons working in conditions of crowding). As a rule, the duration of secondary prevention should be: a) for persons who have suffered ORL without cardita (arthritis, chorea), at least 5 years after the last attack or up to the age of 18 (on the principle of “which longer”); b) in cases of cured cardita without the formation of heart disease - at least 10 years after the last attack or up to the age of 25 (according to the principle of “which longer”); c) for patients with heart disease (including after surgical treatment) - for life. The most effective dosage form of Benzatin gasylpenicillin is extensillin. Studies conducted at the Institute of Rheumatology of the RAMS and the State Scientific Center for Antibiotics have shown that extensillin has obvious pharmacokinetic advantages in comparison with bicillin - 5 in the main parameter - the duration of maintaining adequate anti -stroopoccal concentration of gasylpenicillin in blood serum. From domestic drugs, Bicillin -1 is recommended, which is prescribed in the above doses once every 7 days. Currently, Bicillin -5 (a mixture of 1.2 million. Benzatin Benzilpenicillin and 300 thousand units of novocaine salt of gasolpenicillin) is considered as not complies with pharmacokinetic requirements for preventive drugs, and is not acceptable for a full -fledged secondary prevention of the ORL. The previously previously practiced daily use of erythromycin in patients with the ORL in the history and intolerance of B -lactam antibiotics today needs to revise the widespread increase in BGS resistance to macrolides. As an alternative to this category of patients, timely course treatment with macrolides of each case of BGSA -Tonzillitis/pharyngitis can be considered. It should be emphasized that a scheme for taking antibiotics prescribed for the purpose of preventing the relapse of ORL does not correspond to this for the prevention of IE. In addition, in these patients, especially with prolonged oral administration of penicillin preparations, there is a high probability of caring green streptococci, which are relatively resistant to antibiotics of this group. In such situations for the prevention of IE, it is recommended to prescribe clindamycin. Despite the fact that new antibacterial agents that have appeared in recent years have significantly expanded the possibilities of BGSA -Tonzillite antimicrobial therapy, they did not solve this problem completely. In this regard, many researchers have high hopes for a vaccine containing epitopes of M -Proteins of highly vigilant BGS -stamps that do not enter into a cross reaction with tissue antigens of the human body. Recently, the first data of clinical trials of a 26 -band vaccine containing epitopes of M -Proteins of the so -called “rheumatogenic” BGS strains, which did not enter into a cross reaction with the tissue antigens of the human body, were published. The results of studies with the participation of 30 healthy volunteers have shown that the created recombinant vaccine against A - Stryptococcus stimulates the immune response without any signs of toxicity. According to the creators, it is able to protect against most A -grirtococcal strains, including causing acute tonsillitis, streptococcal toxic shock syndrome and non -roting fascia [15]. The mentioned results inspire a certain optimism, but at the same time at least one question arises: will the patient’s immune system be activated by the vaccine to the primary or re -attack of the ORL? The answer, in all likelihood, should be obtained in further large -scale prospective studies.

References 1. Wannamaker LW Perplexity and precision in the diagnosis of streptococcal pharyngitis. Am J Dis Child 1972; 124:352–358. 2. Bogomilsky M.R. Pediatric otorhinolaryngology. M., Geotar-Media, 2006. 432 p. 3. Nasonova V.A., Belov B.S., Strachunsky L.S. and others. Antibacterial therapy of streptococcal tonsillitis (tonsillitis) and pharyngitis. Ross. Rheumatology 1999; 4; 20 – 27. 4. Belov B.S. A – streptococcal tonsillitis: clinical significance, issues of antibacterial therapy. Attending Physician 2002; 1–2: 24–28. 5. McIsaac W.J., Goel V., To T., Low DE The validity of a sore throat score in family practice. CMAJ 2000; 163(7): 811–815. 6. Denny FW, Wannamaker LW, Brink WR et al. Prevention of rheumatic fever: treatment of the preceding streptococcal infection. JAMA 1950; 142: 151–153. 7. Wannamaker LW, Denny FW, Perry WD et al. Prophylaxis of acute rheumatic fever by treatment of the preceding streptococcal infection with various amounts of depot penicillin. Am J Med 1951; 10: 673–695. 8. Bergman A., Werner R. Failure of children to receive penicillin by mouth. N.Engl.J.Med 1963; 268:1334– Brook I., Gober AE Persistence of group A beta–hemolytic streptococci in toothbrushes and removable orthodontic appliances following treatment of pharyngotonsillitis. Arch Otolaryngol Head Neck Surg 1998;124(9):993–9951338. 9. Roos K., Holm SE, Grahn-Hakansson E., Lagergren L. Recolonization with selected alpha-streptococci for prophylaxis of recurrent streptococcal pharyngotonsillitis—a randomized placebo-controlled multicentre study. Scand J Infect Dis 1996;28(5):459–462. 10. Pichichero ME, Marsocci SM, Murphy ML, et al. Incidence of streptococcal carriers in private pediatric practice. Arch Pediatr Adolesc Med 1999;153(6):624–628. 11. Sela S., Barzilai A. Why do we fail with penicillin in the treatment of group A streptococcus infections? Ann Med 1999; 31: 303–307. 12. Kaplan EL, Chhatwal GS, Rohde M. Reduced ability of penicillin to eradicate ingested group A streptococci from epithelial cells: clinical and path genetic implications. Clin Infect Dis 2006; 43(11): 1398–1406. 13. Seppala H., Klaukka T., Vuopio-Varkila J., et al. The effect of changes in the consumption of macrolide antibiotics on erythromycin resistance in group A streptococci in Finland. N.Engl. J Med 1997; 337 (7): 441–446. 14. Kozlov R.S., Sivaya O.V., Shpynev K.V. et al. Antibiotic resistance of Streptococcus pyogenes in various regions of Russia: results of a multicenter prospective study PeGAS-I. Wedge. microbiol. antimicrobial chemotherapy 2005; 7(2): 154–166. 15. McNeil SA, Halperin SA, Langley JM, et al. Safety and immunogenicity of 26–valent group A streptococcus vaccine in healthy adult volunteers. Clin Infect Dis 2005; 41: 1114–1122. 16. Casey JR, Pichichero ME Higher dosages of azithromycin are more effective in treatment of Group A streptococcal tonsillopharyngitis. Clin Infect Dis 2005; 40: 1748–1755.

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Rheumatism is an infectious-allergic disease with primary damage to the heart and blood vessels.

The basis for the prevention of rheumatism is increasing the body's resistance to streptococcal infection and timely combating it. There are primary and secondary prevention of rheumatism.

Primary prevention includes systematic general strengthening measures: hardening the body, physical education and sports, water treatments, adherence to work and rest schedules, improving living conditions, balanced nutrition, staying in the fresh air, giving up bad habits (alcohol, smoking), reducing contacts if possible. with patients with streptococcal infection, timely and correct treatment of acute and chronic streptococcal infections.

Early diagnosis of streptococcal diseases is often difficult, as it is associated with the need for additional bacteriological and serological studies. It must be taken into account that the typical picture of streptococcal diseases is found in no more than a quarter of patients. In other cases, erased, sometimes asymptomatic forms are observed. A high probability of a streptococcal nature of nasopharyngeal infections is indicated by sore throat, hyperemia of the pharynx with a reaction of regional lymph nodes, leukocytosis, detection of streptococcus in a pharynx smear, streptococcal antigen in the blood, an increase in titers of streptococcal antibodies in the 2-3rd week from the onset of infection.

Due to the fact that rheumatism most often develops after an acute streptococcal infection (tonsillitis, pharyngitis, scarlet fever), its timely diagnosis and vigorous antibiotic therapy are important. Timely and correct treatment of acute respiratory viral infections with mixed infection (virus and streptococcus) is also important.

Along with the treatment of acute streptococcal infections, an important preventive measure is the treatment of chronic streptococcal infections: tonsillitis, pharyngitis, sinusitis, sinusitis. Treatment of multiple dental caries and periodontitis should also be carried out.

Primary prevention should be carried out especially carefully for children, adolescents and young people from families in which there are patients with rheumatism, since these individuals are more susceptible to the threat of rheumatism than others.

secondary prevention is of great importance in the prevention of repeated attacks of rheumatism . Direct prevention is carried out by doctors - cardiorheumatologists.

The method of drug (secondary) prevention of rheumatism consists in the administration of long-acting penicillin in combination with the administration of an anti-inflammatory drug, which achieves an impact on the two main links in the pathogenesis of rheumatism - streptococcal infection and altered reactivity of the body.

Timely and competently carried out primary and secondary prevention of rheumatism significantly reduces the number of relapses and, accordingly, reduces the disability of patients.

Rheumatism in children: current state of the problem

Rheumatism , or acute rheumatic fever

according to the International Classification of Diseases (ICD), is a systemic inflammatory disease of connective tissue with a predominant localization of the process in the cardiovascular system, developing in connection with acute streptococcal infection in persons predisposed to it, mainly at the age of 7–15 years. While not a widespread disease, rheumatism nevertheless represents a serious problem in cardiorheumatology due to the frequent formation of heart defects and the development of temporary and permanent disability. In accordance with ICD-10, acute rheumatic fever is classified as a disease of the circulatory system (class IX) under the codes:

100 – Rheumatic fever without mention of cardiac involvement;

101 – Rheumatic fever with cardiac involvement;

102 – Rheumatic chorea.

Rheumatism was known already in the 5th century BC. Hippocrates in his work “The Four Books of Diseases” wrote: “With arthritis, fever appears, acute pain seizes all the joints of the body, and these pains are sometimes sharper, sometimes weaker, affecting first one or the other joint.” In ancient times, doctors believed that inflammation in the joints was caused by some toxic liquid spreading throughout the body. This is where the name of the disease came from - “rheumatism” (from the Greek “rheum” - flow). Damage to the cardiovascular system was considered a complication of articular syndrome. Only after the publication of the outstanding works of the French doctor Buyot (1836) and the Russian doctor I.G. Sokolsky (1838), rheumatism was identified as an independent disease involving heart damage.

Over more than a century and a half of studying this serious, often disabling disease, the connection between its development and streptococcal infection has been determined, and a system of diagnosis, treatment and prevention has been developed and implemented. This contributed to a widespread decline in the incidence of rheumatism by the middle of the twentieth century. However, in recent years, due to a number of negative socio-economic processes, there has been a tendency towards an increase in the incidence of rheumatism in all age groups, and more intensely in children

. This trend is also due to the presence of secular rhythms characteristic of aggressive streptococcal infections and a decrease in the sensitivity of streptococci to penicillins. The study of the dynamics of the epidemic process shows that in the last decade, streptococcal infection has appeared and is growing, which is an analogue of that of past times, which can contribute to the increase and severity of rheumatism. Therefore, in the future, the problem of rheumatism will not lose its relevance.

Etiology and pathogenesis

The development of rheumatism is closely related to a previous acute or chronic nasopharyngeal infection caused by group A beta-hemolytic streptococcus

.
A special role is given to M protein
, which is part of the streptococcal cell wall. Of the more than 80 known varieties of M protein, M-5, M-6, M-18 and M-24 are considered so-called rheumatogenous. In this case, a stable hyperimmune response to various streptococcal antigens is determined with the formation of antibodies - antistreptolysin O (ASL-O), antistreptohyaluronidase (ASH), antideoxyribonuclease, etc.

Genetic factors play an important role

, which is confirmed by the more frequent incidence of the disease in children from families in which one of the parents suffers from rheumatism.
The importance of genetic factors is to a certain extent evidenced by the results of studying the association of histocompatibility antigens, which revealed, in particular, the frequent occurrence of Dr5–Dr7, Cw2–Cw3 and a number of others in patients with different forms of rheumatism. The genetic marker of this disease, according to a number of researchers, is the B-lymphocyte alloantigen
, determined using monoclonal antibodies D8/17, which is found with high frequency both in patients with rheumatism and in their close relatives. It is associated with a hyperimmune response to streptococcal antigen.

In the pathogenesis of rheumatism, the direct or indirect damaging effects of streptococcal components and its toxins on the body with the development of immune inflammation are of no small importance. Anti-streptococcal antibodies that cross-react with heart tissue (molecular mimicry)

.

Morphological changes

reflect systemic disorganization of connective tissue, especially the cardiovascular system with specific necrotic-proliferative reactions (Ashoff-Talalaev granulomas) and nonspecific exudative manifestations. The latter are more distinct in childhood, which determines the greater (compared to adults) severity and activity of the process, the severity of carditis and other manifestations of rheumatism.

Clinical picture

Rheumatism in children is characterized by a variety of clinical manifestations and variability of course. As a rule, it occurs at school age, less often in preschoolers

and practically does not occur in children under 3 years of age.

In typical cases, the first signs of rheumatism are detected 2–3 weeks after a sore throat or pharyngitis

in the form of fever, symptoms of intoxication, articular syndrome, carditis and other manifestations of the disease. It is also possible for the disease to have asymptomatic onset with the appearance of fatigue, low-grade fever, in the absence of noticeable disorders of the joints or heart, which can be mistakenly regarded as residual effects of a previous infection.

Joint syndrome

One of the earliest signs of rheumatism is articular syndrome (arthritis or arthralgia), detected in 60–100% of affected children. Rheumatoid arthritis is characterized by an acute onset, involvement of large or medium-sized joints (usually knee, ankle, elbow) in the form of mono- or oligoarthritis, volatility of the lesion, and rapid reversal of the process. Articular syndrome relatively rarely develops in isolation at the onset of the disease; more often it is accompanied by cardiac disorders.

Heart damage

Symptoms of heart damage ( carditis

) are determined in 70–85% of cases at the onset of the disease and somewhat more often during subsequent attacks, depending on the predominant localization of the process in the myocardium, endocardium, and the degree of involvement of the pericardium. Due to the difficulty of identifying signs of damage to one or another lining of the heart, the term “rheumatic carditis” is used in practice.

Complaints of a cardiac nature (pain in the heart, palpitations, shortness of breath) are observed in children mainly with severe cardiac disorders. More often, especially at the onset of the disease, various asthenic manifestations (lethargy, malaise, increased fatigue) are observed.

The first objective signs of rheumatic carditis are: disturbance of heart rate (tachycardia, less often - bradycardia); increase in heart size, predominantly to the left; muffled heart sounds, the appearance of systolic murmur.

Character of systolic murmur

, its localization is determined by the degree of involvement of the myocardium and endocardium in the process.
With myocarditis
, the murmur is usually weak or moderate and rarely extends beyond the heart.
In case of endocarditis
with the most characteristic lesion of the mitral valve in rheumatism (valvulitis), a prolonged blowing systolic murmur is heard with a maximum at the apex and at Botkin's point, intensifying on the left side and during exercise, conducted outside the heart. It is mitral valve valvulitis that plays the main role in the formation of valvular heart defects, the development of which can be established no earlier than 6 months from the onset of the disease. The development of rheumatic carditis may be accompanied by circulatory failure, usually not exceeding stage I.

On ECG

with rheumatic carditis, rhythm disturbances are often detected (tachy- or bradyarrhythmia, migration of the pacemaker, sometimes extrasystole, atrial fibrillation),
slowing of atrioventricular conduction
, mainly of the first degree, disturbances in ventricular repolarization, prolongation of electrical systole.

The phonocardiogram (PCG) records a decrease in the amplitude of the first tone at the apex and an increase in the amplitude of the third and fourth sounds. In case of myocarditis, FCG reveals a systolic murmur that is not associated with the first sound, variable in different cardiac cycles, and having a medium-amplitude, medium-frequency character. Mitral valve valvulitis is manifested by high-frequency pansystolic or protosystolic murmur of varying amplitude.

X-ray

in addition to the not always pronounced enlargement of the heart, signs of decreased tonic and contractile function of the myocardium, mitral (with valvulitis of the mitral valve) or aortic (with damage to the aortic valve) configuration of the heart are determined.

When performing an echocardiography, thickening, “shaggy” echo signal from the leaflets of the affected valves, a decrease in their excursion, signs of impaired myocardial contractile function and a number of other symptoms are revealed. With rheumatic carditis in children, the development of pericarditis is also possible, the clinical manifestations of which are determined much less frequently than instrumental signs on the ECG and especially EchoCG.

Currently, with timely treatment, primary rheumatic carditis ends in recovery in most children. The formation of valvular heart defects, often with the development of mitral insufficiency, is determined in 15–18% of cases during the first attack, mainly in severe, protracted or latent course of the disease.

With repeated attacks, which, according to the recommendation of the American Heart Association (AHA), are considered as a new episode of acute rheumatic fever, and not a relapse of the first, the formation of heart defects, often in the form of combined and/or combined valvular lesions, reaches 100%. Due to rheumatic carditis, the formation of prolapse of the mitral (less often aortic) valves

, development
of myocardiosclerosis
with rhythm and conduction disturbances (extrasystole, atrial fibrillation, complete atrioventricular block), as well as
adhesive pericarditis
. Severe rheumatic carditis, its relapses, the presence of myocardiosclerosis, and heart defects contribute to the development of persistent heart failure, leading to disability in patients and possible death.

Small chorea is characteristic of childhood rheumatism

, occurring
in 12–17% of cases
, mainly in early puberty and in girls. Classic symptoms of minor chorea: hyperkinesis, hyper- or hyporeflexia, muscle hypotonia, impaired coordination of movements, changes in psychological state and various autonomic disorders.

The disease begins acutely or, more often, gradually. Children develop emotional lability, irritability, changeable mood, tearfulness, absent-mindedness, memory loss, and deterioration in academic performance. An objective examination reveals involuntary twitching of the muscles of the face and limbs with grimacing, jerky, awkward movements; slurred, unclear speech, changes in handwriting, gait, which makes feeding, dressing, and learning difficult. Hyperkinesis is often bilateral in nature, intensifies with excitement, weakens during sleep until it stops completely.

Often, minor chorea precedes the development of rheumatic carditis or proceeds without clear disturbances in cardiac activity, and is characterized by a torpid course and a tendency to relapse.

Other symptoms

Rarer symptoms of rheumatism include annular rash and rheumatic nodules

.

Annular rash

(ring-shaped erythema) - pale pink, dim rashes in the form of a thin ring-shaped rim, which do not rise above the surface of the skin and disappear with pressure. It is found in 7–10% of children with rheumatism, mainly at the height of the disease and is usually unstable.

Subcutaneous rheumatic nodules

– round, dense, inactive, painless, single or multiple formations localized in the area of ​​large and medium-sized joints, spinous processes of the vertebrae, in tendons, on the aponeurosis. Currently, they are rare, mainly in severe forms of rheumatism, lasting from several days to 1–2 months.

Abdominal syndrome, damage to the lungs, kidneys, liver and other organs due to rheumatism in children is now extremely rare, mainly in severe cases.

Laboratory indicators

Laboratory indicators in patients with rheumatism reflect signs of streptococcal infection, the presence of inflammatory reactions and an immunopathological process. In the active phase, the following are determined: leukocytosis with a shift to the left, an increase in ESR, and often anemia; increased levels of seromucoid, diphenylamine reaction; dysproteinemia with hypergammaglobulinemia; increased titers of ASH, ASLO, increased immunoglobulins class A, M and G; C-reactive protein (CRP), circulating immune complexes, anticardiac antibodies.

Diagnostics

As is known, there are no specific tests for diagnosing rheumatism. In practice, the syndromic method of assessing the status of the patient

, the principle of which was proposed in 1940 by the domestic pediatrician A.A. Kisel.
The author identified such syndromes pathognomonic for rheumatism as migratory polyarthritis, carditis, chorea, annular erythema, and rheumatic nodules as the main diagnostic criteria. Later, A.I. Nesterov made additions to the criteria, and for a long time, when establishing the diagnosis of rheumatism, doctors used the Kisel-Jones-Nesterov criteria. Subsequently, this scheme was repeatedly modified, and currently, in accordance with WHO recommendations, the Jones diagnostic criteria
, revised by the AKA in 1992, are used as international criteria for acute rheumatic fever (Table 1).

The detection of two major or one major and two minor criteria in a patient, combined with data documenting a previous infection with group A streptococci, indicates a high probability of acute rheumatic fever. However, in the early stages, nosological diagnosis in conditions of vague and nonspecific symptoms presents certain difficulties.

The final diagnosis is often established after a thorough differential diagnosis and dynamic observation of the patient with assessment of the results of the therapy.

Differential diagnosis

The differential diagnosis of rheumatism is carried out with a large group of conditions and diseases occurring with articular syndrome (reactive arthritis, juvenile rheumatoid arthritis, Lyme disease, leukemia, neoplastic processes); with a number of inflammatory cardiac diseases (non-rheumatic carditis, infective endocarditis); congenital and acquired disorders of the heart structure (mitral valve prolapse, congenital mitral valve insufficiency or anomaly of its development); autonomic dystonia syndrome. The diagnosis of minor chorea requires, first of all, the exclusion of thyroid hyperkinesis in children, Tourette's syndrome, and chorea in systemic lupus erythematosus.

The formulation of the diagnosis and, accordingly, treatment is carried out on the basis of the classification developed by A.I. Nesterov and the nomenclature of rheumatism (Table 2).

Determining the degree of process activity

(I, II, III) is carried out taking into account the severity of clinical and laboratory manifestations.
The acute course
reflects the rapid development of rheumatism, polysyndromic nature, and vivid clinical and laboratory manifestations (duration – 2–3 months).
The subacute course
may (at its onset) resemble an acute one or is characterized by a slower onset of the disease, less pronounced clinical and laboratory manifestations (duration – up to 6 months).
The protracted course is characterized by moderate signs of activity, torpidity to the therapy (duration - more than 6 months). With a relapsing course,
polysyndromic nature, severity of clinical manifestations, and relapses are noted. The latent course is characterized by the progression of heart disease in the absence of signs of process activity.

Treatment

Treatment of rheumatism in children is based on the early administration of complex therapy aimed at suppressing streptococcal infection and the activity of the inflammatory process, preventing the development or progression of heart disease. The implementation of these programs is carried out according to the principle of stages: 1st stage - inpatient treatment, 2nd stage - follow-up treatment in a local cardio-rheumatological sanatorium, 3rd stage - dispensary observation in a clinic.

Stage 1

At the 1st stage in the hospital, the patient is prescribed drug treatment (antibacterial, antirheumatic and symptomatic), nutritional correction and physical therapy, which are determined individually taking into account the characteristics of the disease and, above all, the severity of carditis. Due to the streptococcal nature of rheumatism, etiotropic therapy is carried out with penicillin

.
Antirheumatic therapy involves one of the nonsteroidal anti-inflammatory drugs (NSAIDs
), which are prescribed alone or in combination with
glucocorticosteroid hormones (GCS)
, depending on the indications (Table 3).

Antibacterial therapy

penicillin is carried out for 10–14 days. In the presence of chronic tonsillitis, frequent exacerbations of focal infection, the duration of treatment with penicillin is increased, or another antibiotic is additionally used - amoxicillin, macrolides (azithromycin, roxithromycin, clarithromycin), cefuroxime axetil, and other cephalosporins in an age-specific dosage.

NSAIDs

apply for at least 1–1.5 months until signs of process activity are eliminated.
Prednisolone
in the initial dose is prescribed for 10–14 days until a clinical effect is obtained, then the daily dose is reduced by 2.5 mg every 5–7 days under the control of clinical and laboratory parameters, and subsequently the drug is discontinued.

Duration of treatment with quinoline drugs

for rheumatism, it ranges from several months to 1–2 years or more, depending on the course of the disease.

Chronic foci of infection are also sanitized in a hospital setting.

, in particular, tonsillectomy, carried out 2–2.5 months from the onset of the disease in the absence of signs of process activity.

Stage 2

The main task at the second stage is to achieve complete remission and restore the functional capacity of the cardiovascular system of children with rheumatism. In the sanatorium, the therapy started in the hospital is continued, foci of chronic infection are sanitized, and the appropriate treatment and health regimen is carried out with differentiated physical activity, physical therapy, and hardening procedures.

Stage 3

The third stage of complex therapy for rheumatism involves the prevention of relapses and progression. For this purpose, long-acting penicillin

, mainly bicillin-5, the first administration of which is carried out during the period of hospital treatment, and subsequently - 1 time every 2-4 weeks year-round. Regularly, 2 times a year, an outpatient examination is carried out, including laboratory and instrumental methods; prescribe the necessary health measures and physical therapy. For children who have had rheumatic heart disease and have valvular heart disease, bicillin prophylaxis is carried out until they reach the age of 21 years or more. For rheumatism without cardiac involvement, bicillin prophylaxis is carried out for 5 years after the last attack. In the spring-autumn period, along with the administration of bicillin, a monthly course of NSAIDs is indicated.

Prevention of rheumatism is divided into primary and secondary.

Primary prevention

is aimed at preventing rheumatism and includes:

1. Increasing immunity (hardening, alternating exercise and rest, good nutrition, etc.).

2. Detection and treatment of acute and chronic streptococcal infections.

3. Preventive measures for children predisposed to the development of rheumatism: from families in which there are cases of rheumatism or other rheumatic diseases; often suffer from nasopharyngeal infection; having chronic tonsillitis or having had an acute streptococcal infection.

Secondary prevention

is aimed at preventing relapses and progression of the disease in children with rheumatism under conditions of clinical observation (see earlier: “Third stage of therapy”).

Key Concepts

Rheumatism is a disease that develops in connection with a streptococcal infection, mainly at the age of 7–15 years. It is characterized by polymorphism of clinical manifestations and variability of course.

The clinical picture of the disease is primarily characterized by heart damage, articular syndrome and minor chorea; Its other manifestations are less common. Cardiac symptoms are caused by the predominance of endo- or myocardial damage with the possible, but more rare, development of pericarditis. A characteristic feature of rheumatic carditis is the development of mitral valve valvulitis. Articular syndrome is often determined already at the onset of the disease in the form of unstable arthritis or arthralgia. The priority of rheumatism in children is minor chorea, which has quite characteristic clinical symptoms.

Primary rheumatism with timely treatment usually ends in recovery. The development of heart defects, as a rule, is manifested by mitral insufficiency with the possibility of subsequent addition of other valvular disorders. Repeated attacks of rheumatism much more often lead to the formation of heart defects.

Treatment of children with rheumatism is carried out on the basis of the principles of staged therapy, depending on the nature of the existing pathology, the degree of activity of the process and the characteristics of its course. For these purposes, antibiotics, NSAIDs, and glucocorticosteroids are used.

An integral part of preventive measures for rheumatism is primary and secondary prevention, aimed at preventing the development of the disease, the occurrence of relapses and the progression of the pathological process.
Literature
1. Belov B.S. “Modern aspects of diagnosing acute rheumatic fever in adolescents.” Det. rheumat. 1996; 2.

1. Belov B.S. “Modern aspects of diagnosing acute rheumatic fever in adolescents.” Det. rheumat. 1996; 2.

2. Belov B.S. “Modern aspects of acute rheumatic fever” Lecture for doctors. Moscow, 1998.

3. Dolgopolova A.V., Kuzmina N.N. “Primary rheumatic carditis in children.” M., Medicine, 1978.

4. Kuzmina N.N. “The problem of rheumatism in children at the present stage.” Det. Rheumat., 1996; 2.

5. Nasonova V.A., Kuzmina N.N., “Rheumatism” in the book. “Rheumatic diseases” (a manual for doctors edited by Nasonova V.A., Bunchuk N.V.). M., “Medicine”, 1997.

6. Nesterov A.I. "Rheumatism". M., Medicine, 1973.