Acute rheumatic fever: symptoms and treatment

Author:

Chekaldina Elena Vladimirovna otorhinolaryngologist, Ph.D.

Quick Transition Treatment of Acute Rheumatic Fever

In some cases, consultation with a cardiologist or neurologist is required.

Acute rheumatic fever (ARF) is a non-purulent complication that occurs 2-4 weeks after streptococcal tonsillopharyngitis.

Streptococcal tonsillopharyngitis (hereinafter referred to as GABHS-pharyngitis) is an acute infectious disease affecting the lymphoid apparatus and the pharyngeal mucosa.

Of particular danger are complications of GABHS pharyngitis, which are divided into:

early (purulent), developing on the 4-6th day from the onset of the disease - otitis media, sinusitis, peritonsillar abscess, cervical lymphadenitis, pneumonia, etc.;
late (non-purulent) - acute rheumatic fever, post-streptococcal glomerulonephritis, toxic shock.

Epidemiology of ARF

Acute rheumatic fever and rheumatic heart disease are called diseases of poverty and economic disadvantage. Complications caused by GABHS are the leading cause of death from cardiovascular disease in people under 50 years of age living in developing countries. ARF can occur at any age.

Worldwide, there are approximately 470,000 new cases of ARF and 275,000 deaths associated with rheumatic heart disease each year.

Most often, ARF occurs in children aged 5 to 15 years. ARF develops in 0.5-3% of cases if GABHS pharyngitis is not treated.

The problem of rheumatic fever in children at the beginning of the 21st century

The article highlights issues related to the prevalence and primary incidence of LC in children, a more favorable course of the disease, improvement of its diagnosis, treatment and prevention, which contributed to a decrease in the frequency of recurrence and progression of the pathological process, as well as a decrease in the percentage of heart disease formation.

According to modern views, rheumatic fever (RF) is a systemic connective tissue disease with a predominant localization of the process in the cardiovascular system, developing after infection with group A β-hemolytic streptococcus in predisposed individuals, mainly children and adolescents 7-15 years old. RL is caused by the development of an autoimmune response to streptococcal epitopes and cross-reactivity with similar epitopes of human tissue (V. A. Nasonova, Y. Stollerman, 1997).

According to generalized WHO data (1989), the prevalence of LC among children in various regions of the world in the 80s was 0.3-18.6 per 1000 schoolchildren, while in previous decades a study conducted by the WHO group in developing countries at the end of the twentieth century , allowed us to state that this parameter, varying in individual areas, averaged 2.2 per 1000 school-age children. According to the same source (WHO-1989), rheumatic heart disease (RHD) is still the main cause of death for young people.

As for the primary incidence of rheumatism, according to WHO (1989), it began to decline in economically developed countries in the mid-twentieth century, with the most pronounced decrease in the increase in the incidence of rheumatism observed over the past 30 years. In the 1980s, the prevalence of the disease was five people per 100,000 population.

The incidence of rheumatism in the Russian Federation, which has also been declining over the past decades, currently averages 0.3 per 1000 children (1990) (from 0.2 to 0.8, according to N. N. Kuzmina et al., 1996).

However, it would be premature to claim that rheumatism has been completely eliminated. This is evidenced by outbreaks of the disease observed over the last decade in the USA and other countries, including Russia (Adanja et al., 1991, Bisno et al., 1993, R. Veasy et al., 1994, 2000; O. M. Folomeeva, 1996).

It should be noted that outbreaks of LC in economically developed countries came as a complete surprise not only to general practitioners, but also to rheumatologist specialists.

Etiology and pathogenesis

According to the experience accumulated in the world of rheumatology, there is a clear connection between upper respiratory tract infection caused by group A β-hemolytic streptococcus and the subsequent development of acute rheumatism. It has been established that streptococcus has a multifaceted effect on the body, although the pathogenetic mechanisms leading to the onset of the disease are still not fully understood.

It is believed that with the development of streptococcal infection, especially massive ones, a large number of different cellular and extracellular antigenic toxins, among which the main role is played by the M-protein of the cell wall, which is a virulence factor, has a direct or indirect damaging effect on tissue.

Equally, and perhaps more important, is the presence of epitopes in M-protein molecules that cross-react with human cardiac and renal tissues.

Immune (cellular and humoral) reactions play a major role in the induction of LC. The humoral response to various streptococcal antigens (ASLO, ASA, ASG, etc.) is well known. The pathogenetic effect of these substances is due to the fact that they are capable of damaging various cells and tissues of the body.

At the end of the twentieth century, the presence of other humoral immune reactions in LC was shown, namely, antibodies to cardiolipin of the IgG class.

A new direction was the assessment of the nature of the development of immunopathological reactions in RL in the form of increased levels of IL-II RFNO-R and neopterin, reflecting the activation of monocytes/macrophages and T-lymphocytes in connection with an increase in the level of rIL-2R.

The accumulated medical experience shows that streptococcal exposure alone is not enough for the development of the disease.

The founder of the pediatric school, A. A. Kisel, at the beginning of the twentieth century pointed out the role of family predisposition in the development of rheumatic fever, as evidenced by the familial aggregation of rheumatism, which significantly exceeds the prevalence of the disease in the population. It has been established that the frequency of “familial” rheumatism is undoubtedly influenced by environmental (primarily streptococcal infection) and genetic factors.

In recent years, a hypothesis has been considered according to which the B-lymphocyte alloantigen, detected using monoclonal antibodies D8/17, is associated with susceptibility to rheumatism (YD Zabriskie, 1985; A. Yibotsky et al., 1991, HA Shostak, 1996). According to the listed authors, this alloantigen can be regarded as a genetic marker that determines susceptibility to the disease.

In recent years, new directions have been developed in the study of the pathogenesis of post-streptococcal diseases, including rheumatism (A. A. Totolyan, 1988; E. L. Nasonov, B. Dzhuzenova, 1991, etc.), however, many aspects of this difficult problem are far from final permissions.

Clinical manifestations of LC in children

As the experience accumulated in the world of rheumatology shows, age-related reactivity plays an important role in the occurrence of LC. Thus, 85 - 90% of patients who develop LC for the first time are children and young people aged 3 to 20 years.

The main distinguishing feature of LC in children has always been the presence of a more pronounced exudative component of inflammation, which is reflected in the clinical manifestations of the disease, namely, more frequent damage to the cardiovascular system, accompanied by severe rheumatic carditis, often combined with extensive damage to the valve apparatus, pericardium, involvement into the pathological process of other serous membranes in the form of visceritis, abdominal syndrome, polyserositis, etc. Such patients often experienced circulatory failure and a high percentage of cases of disease outcome in heart disease. In children, extracardiac manifestations, such as polyarthritis, chorea, annular rash, and rheumatic nodules, were more often (compared to adults) detected. Young patients are also characterized by more frequent recurrence of the disease.

The presented data allow us to state that LC in childhood is characterized by polymorphism and polymorphism of clinical manifestations and is more severe than in other age groups.

The clinical picture of the development of LC in children has changed in the last decades of the twentieth century (N.A. Dmitrova, 1986; N.N. Kuzmina, B.P. Shokh, 1991; RM Pope, 1990; RS Williams, 1994; LG Veasv, 1994 and etc.). It is characterized by the onset of the disease mainly at school age, the predominance of a moderate and minimal degree of activity of the inflammatory process, a significant decrease in the severity of carditis, the prevalence of mild and mild cardiac changes without clear signs of circulatory failure. This is due to the fact that the pathological process in this disease in recent years has largely lost its previously expressed exudative character. However, in recent years there has again been a tendency towards worsening cardiac pathology.

The outstanding pediatrician scientist A. A. Kisel (1940) gave a brilliant description of the main manifestations of rheumatism, calling them the absolute symptom complex of the disease. These include: polyarthritis, cardiac damage, chorea, erythema annulare, rheumatic nodules.

Rheumatic carditis

The leading factor in the clinical picture of the disease, determining the severity of its course and outcome, was and remains rheumatic carditis. Today, rheumatic carditis still occurs mainly in children (80 - 85% of cases), while in 1/5 of children it occurs as if in isolation, and in the rest it is combined with polyarthritis or chorea (B.P. Shokh, L.G Medyntseva, 1993).

Early symptoms of primary rheumatic carditis include abnormal heart rate in the form of tachycardia (30 - 40%) and bradycardia (20 - 39%). In 80 - 85% of patients at the onset of the disease there is a moderate expansion of the borders of the heart. At the same time, a weakening of heart sounds is detected, mainly the first tone, which is detected in the vast majority of patients.

Relatively often, with primary rheumatic heart disease, an additional third (40–75%) and less often a fourth (15–25%) sound is detected.

The most constant signs of primary rheumatic carditis include the appearance of systolic murmur. Depending on the predominant damage to the myocardium or valvular endocardium, systolic murmur has different localization, intensity, duration, timbre and conductivity.

Domestic pediatricians identified the component of valvular damage in the general clinical picture of primary rheumatic carditis (A. B. Volovik, 1955; Z. I. Edelman, 1962; E. S. Lepskaya, N. P. Varik, 1974; A. V. Dolgopolova, N. N. Kuzmina, 1978, N. N. Kuzmina, 2000, etc.). This is of fundamental importance, since children with valvulitis have a high risk of developing heart disease. Of particular importance in recognizing valvular lesions is the qualitative characteristics of the first murmur. Thus, with endomyocarditis with damage to the mitral valve, the systolic murmur most often has a blowing tone, is characterized by duration, and is best heard in the projection area of the mitral valve (apex, fifth point). It is often carried out to the left outside the cardiac region, intensifying after exercise. This qualitative characteristic allows it to be interpreted as endocardial.

Ultrasound examination of the heart makes it possible to objectify the signs of valvular damage.

The use of new generation Doppler echocardiography equipment (DEHOG) allowed N.N. Voronina and E.I. Polubentseva (1993–1995) to identify DEHOG criteria for rheumatic endocarditis, which can be successfully applied in any age group. According to their observations, rheumatic endocarditis of the mitral valve has the following symptoms:

marginal thickening, looseness, “shaggyness” of the valve leaflets;
limited mobility of the thickened posterior leaflet;
the presence of mitral regurgitation, the degree of which depends on the severity of the lesion;
small end prolapse (2 - 4 mm) of the anterior or posterior leaflet.

In children with mitral valve valvulitis, especially severe, the ECG often shows disturbances in heart rate, migration of the pacemaker, prolongation of atrioventricular conduction of the first and, less often, second degree, disturbance of bioelectrical processes in the ventricular myocardium.

Practice shows that aortic valve valvulitis is clinically manifested by a “flowing” diastolic murmur heard along the left edge of the sternum.

During the DEHOG study, the following is noted:

thickening, looseness of the echo signal of the aortic valves, which is clearly visible in diastole from the parasternal position and in cross section. More often there is pronounced thickening of the right coronary cusp. Eccentricity index =1;
aortic regurgitation (direction of the jet towards the anterior mitral valve);
high-frequency flutter (flater) of the anterior mitral leaflet due to aortic regurgitation.

An ECG with valvulitis of the aortic valves often shows signs of diastolic overload of the left ventricle.

With primary rheumatic carditis, a pericardial friction rub may appear, but the latter is clinically detected in the modern course of the disease extremely rarely (0.5–1%).

Circulatory failure usually does not exceed the first and much less often the second stages.

One of the most important clinical criteria confirming the presence of primary rheumatic heart disease in a child is the positive dynamics of clinical and paraclinical manifestations of the disease under the influence of active antirheumatic therapy.

It has been established that the outcome of rheumatic carditis is determined by the frequency of heart disease formation. Unlike previous decades, the percentage of cases of heart disease development after primary rheumatic carditis decreased by two and a half times and averaged 20 - 25% (N. N. Kuzmina, B. P. Shokh, 1991, 2000).

Today, in the structure of rheumatic heart defects in children, as in previous years, isolated heart defects predominate, primarily mitral insufficiency; aortic valve insufficiency, mitral-aortic disease and mitral stenosis are less common.

Rheumatoid arthritis

Arthritis, which is the most common manifestation of LC, occurs in 65 - 75% of children during the first attack of the disease. The articular syndrome observed at the onset retains its previously inherent volatility, affects a varying number of predominantly large and medium-sized joints, is characterized by brightness and is short-lived. However, often the articular syndrome is reduced or becomes prolonged.

With repeated attacks, rheumatoid arthritis is less common and is characterized by similar clinical manifestations.

Arthritis, as a rule, is completely cured without leaving any complications.

Chorea

Chorea occurs in 12–17% of patients with rheumatism and mainly affects girls aged 6 to 15 years. The disease most often develops gradually - children experience unstable mood, asthenia, tearfulness, and irritability. Later, the main symptom complex is added, characterized by hyperkinesis, incoordination of movements, and decreased muscle tone.

Hyperkinesis is manifested by chaotic, non-stereotypical violent movements of various muscle groups and is accompanied by impaired handwriting, speech becomes slurred, and movements become awkward. It is difficult for a child to bring a spoon to his mouth and eat and drink independently.

Hyperkinesis, which intensifies in a state of excitement and disappears during sleep, is more often bilateral, less often - unilateral (hemichorrhea). Carrying out coordination tests is difficult. There are patients with severe muscle hypotonia. Minor chorea is often accompanied by symptoms of autonomic dystonia. Today, the severity of the clinical manifestations of chorea has also decreased; the “choric storm” and the “paralytic form” are practically no longer encountered.

Ring-shaped erythema (annular rash) is observed in 7 - 10% of children. It is localized on the skin of the body, less often on the arms and legs.

Rheumatic nodules

Rheumatic nodules have been observed very rarely in recent years, mainly in children with recurrent rheumatism.

As already indicated, damage to internal organs in children with the modern course of rheumatism is rare and manifests itself mainly in the form of abdominal syndrome.

Laboratory data

In the active phase of LC, shifts in inflammatory activity indicators are noted. Thus, in the vast majority of children with a first or repeated attack, an acceleration of ESR, an increase in seromucoid levels, dysproteinemia with a decrease in the amount of albumin and an increase in globulin fractions due to an increase in γ-globulins are observed and, in addition, there is a tendency to leukocytosis.

The study of humoral indicators of immunity indicates an increase in all classes of immunoglobulins A, M, G. Circulating immune complexes are often determined (V. A. Nasonova, 1989).

Diagnosis and diagnostic criteria

It has been established that LC is characterized by a variety of clinical manifestations and variability of the course. This creates undoubted difficulties in recognizing it. That is why, since the research of Sokolsky and Buyo, the improvement of diagnostic criteria for rheumatism, a description of which was presented by the outstanding pediatrician A. A. Kisel in 1940, has not stopped. Somewhat later, RL recognition criteria were formulated by TD Jons (1944).

The diagnostic criteria for LC were subsequently modified by the American Heart Association in 1955 and 1965.

Significant additions to the diagnostic criteria for rheumatism were made by A. I. Nesterov (1963, 1966, 1973). This document is known in our country as the Kisel-Jones-Nesterov criteria.

In 1982, the criteria for rheumatism were again revised by the American Rheumatological Association. Currently, the WHO research group (1992) recommends that the diagnosis of acute rheumatism be based on the following criteria (WHO, 1992).

The presence of two major or one major and two minor criteria indicates a high probability of developing acute rheumatism in the presence of confirmed data on a previous infection caused by group A streptococcus.

The great merit of domestic researchers (A. I. Nesterov, 1973; A. V. Dolgopolova, N. N. Kuzmina, 1978; V. A. Nasonova, I. A. Bronzov, 1978) was the development of complex treatment methods based on knowledge the most important etiopathogenetic features of this disease and providing:

stationary stage;
follow-up treatment at a local rheumatological sanatorium;
dispensary observation.

This scheme has stood the test of time, which is why it still retains its significance to this day.

A modern doctor has a powerful arsenal of antirheumatic drugs, which are prescribed from the first day of rheumatism diagnosis.

1999 marked half a century since the first use of cortisol (E-acetet) in LC. The invention of hormonal drugs is a great achievement of the twentieth century. It has been established that corticosteroids are able to influence factors that provoke the development of allergic and autoallergic reactions, and also have a powerful anti-inflammatory potential and immunomodulatory effect. Over the past 50 years, hormonal drugs have been constantly improved, the use of which, undoubtedly, is associated with an entire era in the treatment of LC, a change in the course of the disease, which made it possible to save many human lives. However, today the initial enthusiasm has given way to a more restrained attitude towards the possibilities of treatment with hormonal agents due to the fact that long-term observations of patients with LC have revealed a sufficient number of adverse reactions, especially from the myocardium, that occur when using corticosteroids. These data indicate that nonsteroidal anti-inflammatory drugs may be the treatment of choice for LC. However, taking into account the distinct anti-inflammatory and desensitizing effect of steroid hormones, pediatricians unanimously came to the conclusion that corticosteroids are still indicated in modern conditions for children with a distinct component of inflammation, that is, with pronounced and moderate carditis, with a maximum or moderate degree of activity of the rheumatic process , as well as in the acute course of the disease.

Initial daily doses of hormones are prescribed at the rate of 0.7 - 1 mg per 1 kg of child weight per day. Their use remains important taking into account the physiological biorhythm of the adrenal cortex. The course of treatment averages 1–1.5 months. Side effects of corticosteroids in children and adolescents include transient increases in blood pressure, excess fat deposition, hypertrichosis, skin changes (dryness, acne, age spots, etc.), menstrual irregularities, changes in the nervous system, and gastrointestinal dysfunction. - intestinal tract, etc. In the last two decades, due to changes in the course of RL, when treating it, pediatricians are increasingly using only non-steroidal anti-inflammatory drugs, primarily Voltaren or its analogues.

Currently, preference should be given to a new class of non-steroidal compounds - cyclooxygenase inhibitors (COX-2) - nimesulide (Nise), which has good anti-inflammatory activity and is less toxic to the gastrointestinal tract. Nise is available in convenient dosage forms (50 mg dispersible tablets, 60 ml suspension in a bottle with a measuring cap) and is well tolerated by children. Nise is used 2-3 times a day at an optimal dose of 1.5 mg per kg of child’s body weight. The maximum daily dose is 5 mg per kg. For children weighing more than 20 kg, it is recommended to prescribe 50 mg 2 times a day.

In the treatment of primary rheumatic carditis with damage to the valvular apparatus, as well as protracted forms of rheumatism, quinoline drugs are still widely used: delagil, plaquenil, etc. (A. V. Dolgopolova, N. N. Kuzmina, 1978; N. N. Kuzmina, 1996, etc.).

Considering the streptococcal etiology of rheumatism, the principle of simultaneous administration of a 10-14-day course of penicillin or its analogues with anti-inflammatory drugs remains in force. In the presence of multiple and often exacerbating foci of infection, the course of penicillin therapy is lengthened, and according to indications, patients already in the hospital are transferred to bicillin injections.

Follow-up treatment in a local rheumatology sanatorium is the most important part of the complex treatment of LC.

The third component of rehabilitation therapy should be clinical observation of patients who have suffered rheumatic carditis. It is postulated that timely initiation of adequate therapy followed by staged treatment and further preventive measures in the vast majority of patients with primary rheumatic carditis (80 - 90%) not only leads to suppression of the rheumatic process, but also prevents the formation of heart disease, that is, promotes practical recovery or complete rehabilitation of the child (A. I. Nesterov, 1973; A. V. Dolgopolova, N. N. Kuzmina, 1978; B. P. Shokh, L. G. Medyntseva, 1993).

Prevention

The LC prevention program includes primary and secondary prevention. Primary prevention includes two stages:

activities to improve the health of children and adolescents;
measures to combat streptococcal infection (early diagnosis and adequate treatment of upper respiratory tract infections caused by group A streptococci). The drug of choice in this case remains penicillin, which is prescribed 750,000 units to preschool children, 1,000,000-1,500,000 units to school-aged patients for 10-14 days or the first 5 days, followed by the administration of bicillin-5 at a dose of 750,000-1 500,000 units to patients twice with an interval of five days. When administered orally, the prescribed dose of phenoxymethylpenicillin or its analogs: oxacillin, ampicillin is 500-750 units per day for preschool children and 1,000,000-1,500,000 units for school-age patients.

According to WHO recommendations (1989), an effective drug in the treatment of nasopharyngeal infection is oral acid-fast penicillin-phenoxymethylpenicillin-ospen, which is prescribed in the same doses as phenoxymethylpenicillin. For patients with allergies, erythromycin may be an acceptable alternative. The semisynthetic macrolide antibiotic azithromycin (sumamed) has been reported to have some advantages over erythromycin. Roxithromycin has a similar effect. Other broad-spectrum antibiotics (eg, cephalosporins) can also effectively eliminate group A streptococcus from the upper respiratory tract.

Secondary prevention, aimed at preventing relapses in people who have had cancer, consists of regular administration of bicillin (long-acting penicillin).

Long-term studies by domestic and foreign authors using follow-up data (V. N. Bisyarina, 1963; N. A. Barybaeva, 1974; L. I. Benevolenskaya, 1971; M. Markowitz, 1962, 1975; V. Chandrashekhar, 1990, etc. .) showed the high effectiveness of bicillin, prescribed for the prevention of relapses of rheumatism in children. The most optimal should be considered year-round prevention, carried out monthly. All children within five years after suffering an attack of rheumatism are prescribed bicillin-5 at a dose of 1,500,000 units once every four weeks for school-age children and adolescents. For preschool children, bicillin-5 is administered at a dose of 750 units once every two weeks.

For patients at high risk of recurrence of the rheumatic process, bicillin-5 should be administered once every three weeks. In recent years, benzathine benzylpenicillin-retarpen and extensillin have been considered one of the most promising long-acting antibiotics.

To prevent LC, extencillin is administered every 21 days, 600,000–1,200,000 units (for children, depending on age). One bottle contains 600,000 units, 1,200,000 and 2,400,000 units.

For secondary prevention, daily oral antibiotics (penicillin and its analogues) are also possible.

Children who have suffered the first attack of rheumatism (arthritis or chorea) without heart damage are given year-round prophylaxis over the next five years. In patients who have undergone primary or recurrent LC with cardiac damage, especially in the presence of signs of emerging or formed heart disease, year-round prophylaxis should be carried out until they reach the age of 18, and, if necessary, longer.

Simultaneously with the implementation of secondary prevention for patients with RL with the addition of acute respiratory infections, sore throat, pharyngitis, ongoing prevention is recommended. The latter involves prescribing a 10-day course of treatment with penicillin.

Bicillin prophylaxis, along with a set of other measures, is a highly effective means of preventing relapses of LC in children.

Thus, modern rheumatology has achieved undeniable success in the fight against LC. It must be emphasized that to date this problem has not been completely resolved. This primarily applies to the “surprises” of streptococcal infection, which, as is known, is characterized by cyclicality. It is assumed that the next outbreak of this infection will be observed in the first half of the 21st century (V.D. Belyakov, 1996), which, in turn, can lead to an increase in RL.

We can only hope that rheumatology, including pediatric rheumatology, which has reached new frontiers and has modern knowledge of the mechanisms of development of streptococcal infection, adequate therapeutic and preventive drugs, as well as prediction methods, will meet these “surprises” fully armed.

Literature:

Voronina N. M. Clinical and echocardiographic characteristics of primary rheumatic carditis and its outcomes in children: Abstract of thesis. Ph.D. dis. 1983. 20 p.
Kuzmina N.N., Amirdzhanova V.N., Dobrovolskaya Z.N. Prevalence of rheumatic diseases in children and the state of children's cardio-rheumatology service in Russia // Children's Rheumatology. 1996. No. 1. P. 3 - 8.
Nasonova V. A., Kuzmina N. N. Rheumatism. - In the book: “Guide to rheumatic diseases”, M.: Medicine, 1997, p. 144 - 160.
Nesterov A.I. Rheumatism. M., Medicine, 1973.
Rheumatism and rheumatic heart disease (WHO study group report), Geneva, 1989.
Folomeeva O. M., Benevolenskaya L. I. Rheumatism in the Russian Federation: statistics and reality // Bulletin of the Russian Academy of Medical Sciences. 1996. No. 11. P. 21 - 24.
Shokh B.P., Medyntseva L.G. Clinical manifestations and outcome of the first attack of rheumatism in children in the 1980s // Klin. revm. 1993. No. 1. P. 12 - 15.
Jones TD The diagnosis of rheumatic fever // JAMA 1944. Vol.126. P. 481 - 484.
Naruba J., Virmani R., Reddy KS, Jandon R. Rheumatic fever. American Registry of Pathology, 1999, Armed Forces Institute of Pathology, Washington.
Stollerman JH Rheumatic fever // Lancet. 1997. 349, 935 - 942.
Williams RC, Klippel JH, Dieppe PA Acute Rheumatic Fever // Rheumatology. Mosby St Louis, Baltimore, Boston, Chicago, London, Philadelphia, Toronto. 1994, 4, 8 - 10.

N. N. Kuzmina, Doctor of Medical Sciences, Professor Institute of Rheumatology of the Russian Academy of Medical Sciences, Moscow

Diagnosis of ARF

To diagnose ARF, the major and minor Jones Criteria developed by the American Heart Association are used.

Five big criteria:

1. Carditis and valvulitis - develops in 50-70% of cases.

Damage to the layers and valves of the heart. Occurs within 3 weeks after GABHS pharyngitis. As a rule, it begins with endocarditis followed by the development of pancarditis; the mitral and aortic valves are most often affected. Disease progression can last for years after ARF and lead to heart failure.

2. Arthritis (migratory polyarthritis) - develops in 35-66% of cases.

Joint inflammation is the earliest manifestation of ARF; it occurs within 21 days after GABHS pharyngitis, lasts 4 weeks and goes away without a trace. The knee, ankle, elbow, and wrist joints are most often affected. Arthritis is migratory in nature - several joints are successively affected.

3. Damage to the central nervous system (rheumatic chorea, Sydenham chorea, “St. Vitus’s dance”) - develops in 10-30% of cases.

Sharp, irregular, involuntary movements of the limbs, muscle weakness, emotional disorders. Occurs 1-8 months after acute GABHS pharyngitis. Facial muscles are more often affected, and speech disturbances may occur. Emotional changes include outbursts of inappropriate behavior, including crying and restlessness. In 17-35% of patients it may develop into obsessive-compulsive disorder.

4. Rheumatic erythema - develops in less than 6% of cases.

A pink or pale red, non-itchy, ring-shaped rash. Localized on the body or limbs, but not on the face. The rash may appear, disappear, or appear again.

5. Subcutaneous nodules - develop in less than 10% of cases.

Dense, painless formations from a few millimeters to 2 cm. They persist for no more than a month. Localization of nodules is often above the bone, on the extensor surfaces, symmetrically. The skin over the nodule is not inflamed and mobile.

Minor criteria:

Arthralgia is pain in the joints.
Fever (above 38.5 °C).
Increased erythrocyte sedimentation rate (ESR) - above 60 mm/h, C-reactive protein (CRP) - above 30 mg/l.
Prolongation of the PR interval on the ECG.

The diagnosis of ARF is established on the basis of:

the fact of having suffered GABHS-pharyngitis - confirmed by a positive rapid test, bacteriological examination at the time of acute infection or an increase in the titer of antistreptolysin-O (ASLO) already during the occurrence of complications;
Jones criteria: 2 major criteria, 1 major and 2 minor criteria, or 3 minor criteria if the patient has previously suffered ARF.

All patients with suspected ARF must undergo an ECG and EchoCG (ultrasound of the heart) to identify morphological changes in the heart valves and signs of pathological regurgitation (backflow of blood). Laboratory tests according to indications (since they are nonspecific) - ESR and CRP. If signs of chorea are present, a neurological examination is necessary.

Rheumatism (rheumatic fever)

Symptoms of rheumatism are extremely polymorphic and depend on the degree of severity and activity of the process, as well as the involvement of various organs in the process. A typical clinical picture of rheumatism is directly related to a previous streptococcal infection (tonsillitis, scarlet fever, pharyngitis) and develops 1-2 weeks after it. The disease begins acutely with low-grade fever (38-39 °C), weakness, fatigue, headaches, and sweating. One of the early manifestations of rheumatism is arthralgia - pain in medium or large joints (ankle, knee, elbow, shoulder, wrist).

With rheumatism, arthralgia is multiple, symmetrical and volatile (pain disappears in some joints and appears in other joints) in nature. There is swelling, swelling, local redness and increased temperature, and a sharp restriction of movement of the affected joints. The course of rheumatic arthritis is usually benign: after a few days the severity of the symptoms subsides, the joints are not deformed, although moderate pain may persist for a long time.

After 1-3 weeks, rheumatic carditis occurs: pain in the heart, palpitations, interruptions, shortness of breath; asthenic syndrome (malaise, lethargy, fatigue). Heart damage due to rheumatism is observed in 70-85% of patients. With rheumatic carditis, all or individual membranes of the heart become inflamed. More often, simultaneous damage to the endocardium and myocardium occurs (endomyocarditis), sometimes with involvement of the pericardium (pancarditis), and isolated myocardial damage (myocarditis) may develop. In all cases of rheumatism, the myocardium is involved in the pathological process.

With diffuse myocarditis, shortness of breath, palpitations, interruptions and pain in the heart, cough during exercise, and in severe cases - circulatory failure, cardiac asthma or pulmonary edema. The pulse is small and tachyarrhythmic. Myocardial cardiosclerosis is considered a favorable outcome of diffuse myocarditis.

With endocarditis and endomyocarditis, the mitral (left atrioventricular) valve is most often involved in the rheumatic process, less often the aortic and tricuspid (right atrioventricular) valves. The clinical picture of rheumatic pericarditis is similar to pericarditis of other etiologies.

With rheumatism, the central nervous system can be affected; a specific symptom in this case is the so-called rheumatic or minor chorea: hyperkinesis appears - involuntary twitching of muscle groups, emotional and muscle weakness. Less common are skin manifestations of rheumatism: ring-shaped erythema (in 7–10% of patients) and rheumatic nodules. Erythema annulare (rash annulare) is a ring-shaped, pale pink rash on the trunk and legs; rheumatic subcutaneous nodules - dense, round, painless, inactive, single or multiple nodules localized in the area of medium and large joints.

Damage to the kidneys, abdominal cavity, lungs and other organs occurs in severe cases of rheumatism, which is extremely rare at present. Rheumatic lung damage occurs in the form of rheumatic pneumonia or pleurisy (dry or exudative). With rheumatic kidney damage, red blood cells and protein are detected in the urine, and a clinical picture of nephritis occurs. Damage to the abdominal organs during rheumatism is characterized by the development of abdominal syndrome: abdominal pain, vomiting, tension in the abdominal muscles. Repeated rheumatic attacks develop under the influence of hypothermia, infections, physical stress and occur with a predominance of symptoms of heart damage.

Treatment of ARF

Eradication of GABHS infection is necessary regardless of whether there are signs of pharyngitis. Antibacterial therapy is carried out similarly to therapy for acute tonsillopharyngitis.

Symptomatic therapy:

arthritis - non-steroidal anti-inflammatory drugs to relieve pain and prevent the involvement of new joints;
carditis - treatment is carried out only if heart failure develops;
chorea - usually does not require treatment, but sometimes it may be necessary to prescribe antipsychotics and anticonvulsants;
erythema and subcutaneous nodules - no treatment.

Prevention of ARF

Primary is timely diagnosis and treatment of GABHS pharyngitis.

Secondary - prevention of new episodes of GABHS infection, including eradication of GABHS even in asymptomatic carriers.

The duration of antibiotic prophylaxis is determined based on the characteristics of the existing pathological process. If we are talking about post-streptococcal arthritis, it can be limited to 1-2 years. In case of ARF without carditis, the duration of taking antibiotics is 5 years or until the patient is 21 years old (whichever is longer), ARF with carditis without consequences is 10 years or up to 21 years old (whichever is longer), ARF with damage to the heart valves is 10 years or up to 40 years old ( whichever is longer), and sometimes for life.

Acute rheumatic fever: modern approaches to primary and secondary prevention

Acute rheumatic fever (ARF) is a post-infectious complication of tonsillitis (tonsillitis) or pharyngitis caused by group A β-hemolytic streptococcus (GABHS), in the form of a systemic inflammatory disease of connective tissue with a predominant localization in the cardiovascular system (carditis), joints (migratory polyarthritis ), brain (chorea) and skin (erythema annulare, rheumatic nodules). ARF develops, as a rule, in predisposed individuals, mainly young people (7–15 years), due to the body's autoimmune response to streptococcal antigens and their cross-reactivity with similar autoantigens of the listed affected human tissues (the phenomenon of molecular mimicry).

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.

ARF and CRHD belong to a group of diseases in the treatment and prevention of which significant progress has been achieved. However, in recent years it has become obvious that the problem of the incidence of ARF and CRHD has not been completely solved.

In particular, in 1994, compared with the previous year, 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. These data echo the non-decreasing incidence (detection) rates of CRHD. 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), and therefore, the awareness of practicing physicians about modern standards of treatment for ARF and CRHD is of particular importance.

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 exposure to fresh air;
rational physical education and sports;
combating overcrowding in homes, preschool institutions, schools, colleges, universities, public institutions;
carrying out 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.

Issues of diagnostics and differential diagnosis of acute and chronic recurrent GABHS tonsillitis/pharyngitis are widely covered in the domestic medical literature, including on the pages of this journal [4]. Within the framework of this article, I would like to emphasize that an accurate diagnosis and mandatory rational antibiotic therapy for GABHS tonsillitis/pharyngitis still play a crucial role both in controlling the spread of this infection and in the prevention of ARF.

Despite the fact that GABHS still retains almost complete sensitivity to β-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%. One of the possible reasons for this phenomenon may be the 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 by 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 [5]. Moreover, an analysis of the causes of the aforementioned outbreak of ARF in the United States 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.

Another equally important reason may be the hydrolysis of penicillin by specific enzymes-β-lactamases, which are produced by microorganisms - co-pathogens (S. aureus, H. influenzae, M. catarrhalis, etc.) present in the deep tissues of the tonsils in 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 beta-lactamases (selective pressing phenomenon). It is shown that by the end of the 20th century. the detection rate of co-pathogens producing β-lactamases in children with chronic recurrent tonsillitis increased to 94% [6].

Penicillin drugs remain the means of choice in the treatment of acute forms of GABHS tonsillitis (Table 1). 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 60%, respectively).

The undoubted advantages include the presence of amoxicillin in a dispersible dosage form - Solutab (Flemoxin Solutab), which has favorable pharmacokinetic properties (high bioavailability, uniform increase in concentrations of the active substance in the blood), minimal impact on the intestinal microflora and, therefore, less frequent dyspeptic disorders. Equally important is the ease of use of this dosage form (swallowing whole, chewing or pre-dissolving in water), which increases patients’ compliance with the treatment regimen.

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, taking into account the availability 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 presence of the following factors:

low patient compliance;
A history of ARF and/or CRHD in close relatives;
unfavorable social and living conditions (overcrowding 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 β-lactam antibiotics, it is advisable to prescribe macrolides (spiramycin, azithromycin, roxithromycin, clarithromycin, josamycin, midecamycin), whose antistreptococcal activity 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. Noteworthy is the drug from the group of 16-membered macrolides, josamycin (Vilprafen, Vilprafen Solutab), which is active against some erythromycin-resistant strains of streptococci and staphylococci and has the above-mentioned advantages of a dispersible dosage form. 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 .

As already indicated, in the presence of chronic recurrent GABHS tonsillitis, the probability of colonization of the site of infection by microorganisms producing β-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 2). 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). It should be noted that a comparative pharmacokinetic study revealed an important advantage of the dispersible dosage form of amoxicillin/clavulanate (Flemoclav Solutab) over the standard tablet drug, which consists in a significant reduction (almost 2 times) in the variability of clavulanic acid concentrations in the blood serum [7], which should help improve treatment tolerance. It has been shown that the administration of Flemoclav Solutab significantly reduces the incidence of diarrhea, which reaches 24% when using conventional forms of amoxicillin/clavulanate [8].

It must be emphasized that the use of tetracyclines, sulfonamides, co-trimoxazole (Biseptol) 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 repeated 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:

patient's age;
presence of CRHD;
time since the first ORL attack;
number of previous attacks;
factor of crowding in the family;
family history of ARF/CRHD;
socio-economic and educational status of the patient;
risk of streptococcal infection in the region;
profession and place of work of the patient (school teachers, doctors, people working in crowded conditions).

As a rule, the duration of secondary prevention should be:

a) for persons who have had ARF without carditis (arthritis, chorea) - at least 5 years after the last attack or until the age of 18 (based on the “whichever is longer” principle);

b) in cases of cured carditis without the formation of a heart defect - at least 10 years after the last attack or until the age of 25 (based on the “whichever is longer” principle);

c) for patients with heart disease (including after surgical treatment) - for life.

The most effective dosage form of benzathine benzylpenicillin is extencillin. Studies conducted at the Institute of Rheumatology of the Russian Academy of Medical Sciences and the State Research Center for Antibiotics have shown that extencillin has clear pharmacokinetic advantages over Bicillin-5 in terms of the main parameter - the duration of maintaining an adequate antistreptococcal concentration of benzylpenicillin in the blood serum of patients. Of the domestic drugs, Bicillin-1 is recommended, which is prescribed in the above doses once every 7 days.

Currently, the drug Bicillin-5 (a mixture of 1.2 million units of benzathine benzylpenicillin and 300 thousand units of procaine salt of benzylpenicillin) is considered as not meeting the pharmacokinetic requirements for preventive drugs and is not acceptable for full secondary prevention of ARF.

The previously widely practiced daily use of erythromycin in patients with a history of ARF and intolerance to β-lactam antibiotics today needs to be revised due to the widespread increase in GABHS resistance to macrolides. As an alternative, timely course treatment with macrolides for each case of GABHS tonsillitis/pharyngitis may be considered in this category of patients.

Literature

Rheumatic fever and rheumatic heart disease/WHO technical report series No. 923. Geneva, 2004. 122 p.
Belyakov V.D. Surprises of streptococcal infection // Vestn. RAMS. 1996; 11:24–28.
Folomeeva O. M., Amirdzhanova V. N., Yakusheva E. O. et al. Incidence of rheumatic diseases in the Russian population (analysis over 10 years) // Ter. arch. 2002. 5: 5–11.
Belov B. S. A-streptococcal tonsillitis: clinical significance, issues of antibacterial therapy. Attending doctor. 2002, 1–2: 24–28.
Bergman A., Werner R. Failure of children to receive penicillin by mouth // N. Engl. J. Med. 1963; 268:1334–1338.
Brook I. The role of beta-lactamase producing bacteria and bacterial interference in streptococcal tonsillitis // Int. J. Antimicrob. Agents. 2001; 17(6): 439–442.
Sourgens H., Steinbrede H., Verschoor JS et al. Bioequivalence study of a novel Solutab tablet formulation of amoxicillin/clavulanic acid versus the originator film-coated tablet // Int. J. Clin. Pharmacol. Ther. 2001, 39, 75–82.
Ushkalova E. A. The importance of dosage forms for rational antibiotic therapy. Dosage form Solutab // Doctor. 2007: 3: 1–4.

B. S. Belov , Doctor of Medical Sciences T. P. Grishaeva Institute of Rheumatology RAMS, Moscow

How is ARF treated at the Rassvet Clinic?

We provide timely diagnosis and adequate treatment of GABHS pharyngitis, which reduces the incidence of ARF by almost 70%. When choosing antibacterial therapy, we always give preference to penicillin antibiotics - as the most effective drugs that have been proven to reduce the incidence of ARF. We never reduce the course of antibiotic therapy when there is clinical improvement. If GABHS pharyngitis is detected, we do not prescribe local treatment (rinses, sprays) to the detriment of systemic antibacterial therapy.

We provide adequate eradication therapy for GABHS in ARF in order to prevent relapses and progression of rheumatic heart disease. We offer a full examination for diagnosed ARF - ECG, ECHO-CG, consultation with a cardiologist and neurologist with the selection of the necessary therapy.